Synthetic biology and metabolic engineering.

Science.gov (United States)

Stephanopoulos, Gregory

2012-11-16

Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

Modeling planarian regeneration: a primer for reverse-engineering the worm.

Directory of Open Access Journals (Sweden)

Daniel Lobo

Full Text Available A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences-using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an

The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom-Programmable Circuits

Science.gov (United States)

2017-03-23

Introduction The widely practiced horizontal integrated circuit supply chain exposes a design to various types of attacks including the reverse engineering ...STT_CMOS designs for reverse- engineering prevention, DAC 2016. [5] M. E. Massad and et. al. Integrated circuit (IC) decamouflaging: reverse...The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom-Programmable Circuits Raza Shafiq Hamid Mahmoodi Houman Homayoun Hassan

Un-Building Blocks: A Model of Reverse Engineering and Applicable Heuristics

Science.gov (United States)

2015-12-01

Inclusion relationships of root events, events, and subevents .................179  Table 5.  Formal specification of reverse engineering model using Monterey...intend to stay technologically competitive at personal as well as societal levels. Third, reverse engineering is important for pedagogical reasons. It is...increasingly blurred (Anderson, 2012).4 Third, reverse engineering can be a pedagogical tool (Otto & Wood, 2000; O’Brien, 2010; Halsmer, 2013

Synthetic biology: an emerging engineering discipline.

Science.gov (United States)

Cheng, Allen A; Lu, Timothy K

2012-01-01

Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

Research regarding reverse engineering for aircraft components

Directory of Open Access Journals (Sweden)

Udroiu Razvan

2017-01-01

Full Text Available Reverse engineering is a useful technique used in manufacturing and design process of new components. In aerospace industry new components can be developed, based on existing components without technical Computer Aided Design (CAD data, in order to reduce the development cycle of new products. This paper proposes a methodology wherein the CAD model of turbine blade can be build using computer aided reverse engineering technique utilising a 5 axis Coordinate Measuring Machine (CMM. The proposed methodology uses a scanning strategy by features, followed by a design methodology for 3D modelling of complex shapes.

Reverse engineering of the robot base platform

International Nuclear Information System (INIS)

Anwar A Rahman; Azizul Rahman A Aziz; Mohd Arif Hamzah; Muhd Nor Atan; Fadil Ismail; Rosli Darmawan

2009-01-01

The robot base platform used to place the robotic arm version 2 was imported through a local company. The robot base platform is used as a reference for reverse egineering development for a smaller size robot. The paper will discuss the reverse engineering design process and parameters involved in the development of the robot base platform. (Author)

Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

Science.gov (United States)

Willing, Ryan; King, Graham J W; Johnson, James A

2015-11-26

Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (pengineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

7th Annual Systems Biology Symposium: Systems Biology and Engineering

Energy Technology Data Exchange (ETDEWEB)

Galitski, Timothy P.

2008-04-01

Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

Application of reverse engineering in the medical industry.

Science.gov (United States)

Kaleev, A. A.; Kashapov, L. N.; Kashapov, N. F.; Kashapov, R. N.

2017-09-01

The purpose of this research is to develop on the basis of existing analogs new design of ophthalmologic microsurgical tweezers by using reverse engineering techniques. Virtual model was obtained by using a three-dimensional scanning system Solutionix Rexcan 450 MP. Geomagic Studio program was used to remove defects and inaccuracies of the obtained parametric model. A prototype of the finished model was made on the installation of laser stereolithography Projet 6000. Total time of the creation was 16 hours from the reverse engineering procedure to 3D-printing of the prototype.

Cranioplasty prosthesis manufacturing based on reverse engineering technology

Science.gov (United States)

Chrzan, Robert; Urbanik, Andrzej; Karbowski, Krzysztof; Moskała, Marek; Polak, Jarosław; Pyrich, Marek

2012-01-01

Summary Background Most patients with large focal skull bone loss after craniectomy are referred for cranioplasty. Reverse engineering is a technology which creates a computer-aided design (CAD) model of a real structure. Rapid prototyping is a technology which produces physical objects from virtual CAD models. The aim of this study was to assess the clinical usefulness of these technologies in cranioplasty prosthesis manufacturing. Material/Methods CT was performed on 19 patients with focal skull bone loss after craniectomy, using a dedicated protocol. A material model of skull deficit was produced using computer numerical control (CNC) milling, and individually pre-operatively adjusted polypropylene-polyester prosthesis was prepared. In a control group of 20 patients a prosthesis was manually adjusted to each patient by a neurosurgeon during surgery, without using CT-based reverse engineering/rapid prototyping. In each case, the prosthesis was implanted into the patient. The mean operating times in both groups were compared. Results In the group of patients with reverse engineering/rapid prototyping-based cranioplasty, the mean operating time was shorter (120.3 min) compared to that in the control group (136.5 min). The neurosurgeons found the new technology particularly useful in more complicated bone deficits with different curvatures in various planes. Conclusions Reverse engineering and rapid prototyping may reduce the time needed for cranioplasty neurosurgery and improve the prosthesis fitting. Such technologies may utilize data obtained by commonly used spiral CT scanners. The manufacturing of individually adjusted prostheses should be commonly used in patients planned for cranioplasty with synthetic material. PMID:22207125

Reverse Engineering Camouflaged Sequential Integrated Circuits Without Scan Access

OpenAIRE

Massad, Mohamed El; Garg, Siddharth; Tripunitara, Mahesh

2017-01-01

Integrated circuit (IC) camouflaging is a promising technique to protect the design of a chip from reverse engineering. However, recent work has shown that even camouflaged ICs can be reverse engineered from the observed input/output behaviour of a chip using SAT solvers. However, these so-called SAT attacks have so far targeted only camouflaged combinational circuits. For camouflaged sequential circuits, the SAT attack requires that the internal state of the circuit is controllable and obser...

Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

Science.gov (United States)

Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

2000-01-01

Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.

14 CFR 23.934 - Turbojet and turbofan engine thrust reverser systems tests.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Turbojet and turbofan engine thrust... CATEGORY AIRPLANES Powerplant General § 23.934 Turbojet and turbofan engine thrust reverser systems tests. Thrust reverser systems of turbojet or turbofan engines must meet the requirements of § 33.97 of this...

Integrating rehabilitation engineering technology with biologics.

Science.gov (United States)

Collinger, Jennifer L; Dicianno, Brad E; Weber, Douglas J; Cui, Xinyan Tracy; Wang, Wei; Brienza, David M; Boninger, Michael L

2011-06-01

Rehabilitation engineers apply engineering principles to improve function or to solve challenges faced by persons with disabilities. It is critical to integrate the knowledge of biologics into the process of rehabilitation engineering to advance the field and maximize potential benefits to patients. Some applications in particular demonstrate the value of a symbiotic relationship between biologics and rehabilitation engineering. In this review we illustrate how researchers working with neural interfaces and integrated prosthetics, assistive technology, and biologics data collection are currently integrating these 2 fields. We also discuss the potential for further integration of biologics and rehabilitation engineering to deliver the best technologies and treatments to patients. Engineers and clinicians must work together to develop technologies that meet clinical needs and are accessible to the intended patient population. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Computer-aided dental prostheses construction using reverse engineering.

Science.gov (United States)

Solaberrieta, E; Minguez, R; Barrenetxea, L; Sierra, E; Etxaniz, O

2014-01-01

The implementation of computer-aided design/computer-aided manufacturing (CAD/CAM) systems with virtual articulators, which take into account the kinematics, constitutes a breakthrough in the construction of customised dental prostheses. This paper presents a multidisciplinary protocol involving CAM techniques to produce dental prostheses. This protocol includes a step-by-step procedure using innovative reverse engineering technologies to transform completely virtual design processes into customised prostheses. A special emphasis is placed on a novel method that permits a virtual location of the models. The complete workflow includes the optical scanning of the patient, the use of reverse engineering software and, if necessary, the use of rapid prototyping to produce CAD temporary prostheses.

Reversibility: An Engineer's Point of View

Energy Technology Data Exchange (ETDEWEB)

Berest, Pierre [LMS, ecole Polytechnique (France)

2012-07-01

Reversibility is the most consistent option in a democratic country. However reversibility may also have several drawbacks which must be identified and mitigated. Reversibility of a geological repository is a relatively new idea in France. The 1991 law dedicated to nuclear waste management considered reversibility as a possible option. Fifteen years later, the 2006 law mandated that a deep repository must be reversible and that the exact content of this notion should be defined by a new law to be discussed by the Parliament in 2015. Reversibility was not a concern put forward by engineers. It clearly originated from a societal demand sponsored and formulated by the Parliament. Since 1991, the exact meaning of this mandate progressively became more precise. In the early days, reversibility meant the technical and financial capability to retrieve the wastes from the repository, at least for some period of time after being emplaced. Progressively, a broader definition, suggested by Andra, was accepted: reversibility also means that a disposal facility should be operated in such a way that a stepwise decision-making process is possible. At each step, society must be able to decide to proceed to the next step, to pause or to reverse a step. Several benefits can be expected from a reversible repository. Some technical safety concerns may be only recognised after waste emplacement. Radioactive wastes may become a resource whose recoverability is desirable. Regulations may change, alternative waste treatment or better disposal techniques may be developed, or the need to modify a component of the facility may arise. Looking back at how chemical or domestic wastes were managed some 50 years ago easily underscores that it is not unreasonable to hope for significant advances in the future. For scientists and engineers, reversibility proves to have several other merits. To design and build a good repository, time is needed. The operator of a mine or of an oil field knows that

Malware analysis and reverse engineering

OpenAIRE

Šváb, Martin

2014-01-01

Focus of this thesis is reverse engineering in information technology closely linked with the malware analysis. It explains fundamentals of IA-32 processors architecture and basics of operating system Microsoft Windows. Main part of this thesis is dedicated to the malware analysis, including description of creating a tool for simplification of static part of the analysis. In Conclusion various approaches to the malware analysis, which were described in previous part of the thesis, are practic...

Reverse engineering of integrated circuits

Science.gov (United States)

Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

2003-01-01

Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

Experimental study of a reverse flow catalytic converter for a duel fuel engine

Energy Technology Data Exchange (ETDEWEB)

Liu, B.; Checkel, M. D. [Alberta Univ., Dept. of Mechanical Engineering, Edmonton, ANB (Canada); Hayes, R. E. [Alberta Univ., Dept, of Chemical and Materials Engineering, Edmonton, AB, (Canada)

2001-08-01

Performance of a reverse flow catalytic converter for a methane/diesel dual fuel engine is evaluated under steady and transient engine conditions. The converter is of the monolith honeycomb type with palladium catalyst washcoat. Results of the reverse flow converter's performance was found to be superior for several steady state engine operations when compared to unidirectional flow operation. In transient operations following a step change in engine operating conditions, reverse flow was found to be better than unidirectional flow when the change in engine operation was such as to reduce the exhaust gas temperature. When exhaust gas temperature was increased, reverse flow decreased the rate of increase in the reactor temperature. Testing was done using the transient Japanese 6-Mode tests. Best results were achieved with a switch time in the five seconds to fifteen seconds range. 31 refs., 9 tabs., 24 figs.

Benefits of reverse engineering technologies in software development makerspace

Directory of Open Access Journals (Sweden)

Aabidi M.H.

2017-01-01

Full Text Available In the recent decades, the amount of data produced by scientific, engineering, and life science applications has increased with several orders of magnitude. In parallel with this development, the applications themselves have become increasingly complex in terms of functionality, structure, and behavior. In the same time, development and production cycles of such applications exhibit a tendency of becoming increasingly shorter, due to factors such as market pressure and rapid evolution of supporting and enabling technologies. As a consequence, an increasing fraction of the cost of creating new applications and manufacturing processes shifts from the creation of new artifacts to the adaption of existing ones. A key component of this activity is the understanding of the design, operation, and behavior of existing manufactured artifacts, such as software code bases, hardware systems, and mechanical assemblies. For instance, in the software industry, it is estimated that maintenance costs exceed 80% of the total costs of a software product's lifecycle, and software understanding accounts for as much as half of these maintenance costs. To facilitate the software development process, it would be ideal to have tools that automatically generate or help to generate UML (Unified Modeling Language models from source code. Reverse engineering the software architecture from source code provides a valuable service to software practitioners. Case tools implementing MDA and reverse-engineering constitute an important opportunity of software development engineers. So MDA and reverse engineering is an important key witch make makerspace more productive and more efficient.

Repeatable Reverse Engineering with PANDA

Science.gov (United States)

2015-12-08

necessary layout information for the Android 2.3 and 4.2 SDK kernels. See Section IV-C for an example of the kind of deep reverse engineering of Android apps ...code re-use and simplifying complex analysis development. We demonstrate PANDA’s effectiveness via a number of use cases, including enabling an old but...continue to function. 2) Identify critical vulnerabilities . 3) Understand the true purpose and actions of code. It is common for legacy code to stop

Reverse electrodialysis heat engine for sustainable power production

International Nuclear Information System (INIS)

Tamburini, A.; Tedesco, M.; Cipollina, A.; Micale, G.; Ciofalo, M.; Papapetrou, M.; Van Baak, W.; Piacentino, A.

2017-01-01

Graphical abstract: State of the art technologies for the conversion of heat into power. Grey circles refer to technologies at very early stage of development and non-available at industrial level. The Carnot efficiency (on the secondary horizontal axis) is evaluated assuming a cold sink temperature of 25 °C. SRC-hot gases: Steam Rankine Cycle integrated with gas turbine/other topping cycles; SRC-fuel: Steam Rankine Cycle directly fuelled by oil, coal or other fuels; KC: Kalina Cycle; ORC: Organic Rankine Cycle; TEG: Thermoelectric Generation; PEPG: Piezoelectric Power Generation with waste heat-powered expansion/compression cycle; OHE: Osmotic Heat Engine; REDHE, Reverse Electrodialysis Heat Engine (this paper). Display Omitted -- Highlights: •For the first time, the potential of Reverse Electrodialysis Heat Engine is assessed. •An overview of the possible regeneration methods is presented. •Performance of the RED unit fed by different salty solutions was suitably optimized. •Three different RED Heat Engine scenarios were studied. •Exergetic efficiency of about 85% could be achieved in the foreseen future. -- Abstract: Reverse Electrodialysis Heat Engine (REDHE) is a promising technology to convert waste heat at temperatures lower than 100 °C into electric power. In the present work an overview of the possible regeneration methods is presented and the technological challenges for the development of the RED Heat Engine (REDHE) are identified. The potential of this power production cycle was investigated through a simplified mathematical model. In the first part of the work, several salts were singularly modelled as possible solutes in aqueous solutions feeding the RED unit and the corresponding optimal conditions were recognized via an optimization study. In the second part, three different RED Heat Engine scenarios were studied. Results show that power densities much higher than those relevant to NaCl-water solutions can be obtained by using different

Android Application Protection against Static Reverse Engineering based on Multidexing

Directory of Open Access Journals (Sweden)

Nak Young Kim

2016-11-01

Full Text Available DEX files are executable files of Android applications. Since DEX files are in the format of Java bytecodes, their Java source codes can be easily obtained using static reverse engineering tools. This results in numerous Android application thefts. There are some tools (e.g. bangcle, ijiami, liapp that protect Android applications against static reverse engineering utilizing dynamic code loading. These tools usually encrypt classes.dex in an APK file. When the application is launched, the encrypted classes.dex file is decrypted and dynamically loaded. However, these tools fail to protect multidex APKs, which include more than one DEX files (classes2.dex, classes3.dex, ... to accommodate large-sized execution codes. In this paper, we propose a technique that protects multidex Android applications against static reverse engineering. The technique can encrypt/decrypt multiple DEX files in APK files and dynamically load them. The experimental results show that the proposed technique can effiectively protect multidex APKs.

Multiplexed Engineering in Biology.

Science.gov (United States)

Rogers, Jameson K; Church, George M

2016-03-01

Biotechnology is the manufacturing technology of the future. However, engineering biology is complex, and many possible genetic designs must be evaluated to find cells that produce high levels of a desired drug or chemical. Recent advances have enabled the design and construction of billions of genetic variants per day, but evaluation capacity remains limited to thousands of variants per day. Here we evaluate biological engineering through the lens of the design–build–test cycle framework and highlight the role that multiplexing has had in transforming the design and build steps. We describe a multiplexed solution to the ‘test’ step that is enabled by new research. Achieving a multiplexed test step will permit a fully multiplexed engineering cycle and boost the throughput of biobased product development by up to a millionfold.

Reversible and irreversible heat engine and refrigerator cycles

Science.gov (United States)

Leff, Harvey S.

2018-05-01

Although no reversible thermodynamic cycles exist in nature, nearly all cycles covered in textbooks are reversible. This is a review, clarification, and extension of results and concepts for quasistatic, reversible and irreversible processes and cycles, intended primarily for teachers and students. Distinctions between the latter process types are explained, with emphasis on clockwise (CW) and counterclockwise (CCW) cycles. Specific examples of each are examined, including Carnot, Kelvin and Stirling cycles. For the Stirling cycle, potentially useful task-specific efficiency measures are proposed and illustrated. Whether a cycle behaves as a traditional refrigerator or heat engine can depend on whether it is reversible or irreversible. Reversible and irreversible-quasistatic CW cycles both satisfy Carnot's inequality for thermal efficiency, η ≤ η C a r n o t . Irreversible CCW cycles with two reservoirs satisfy the coefficient of performance inequality K ≤ K C a r n o t . However, an arbitrary reversible cycle satisfies K ≥ K C a r n o t when compared with a reversible Carnot cycle operating between its maximum and minimum temperatures, a potentially counterintuitive result.

Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

Science.gov (United States)

Liu, Mengjin; Bienfait, Bruno; Sacher, Oliver; Gasteiger, Johann; Siezen, Roland J; Nauta, Arjen; Geurts, Jan M W

2014-01-01

The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

Penerapan Reverse Engineering Dalam Penentuan Pola Interaksi Sequence Diagram Pada Sampel Aplikasi Android

Directory of Open Access Journals (Sweden)

Vierdy Sulfianto Rahmadani

2015-04-01

Full Text Available The purpose of this research is to apply the application of reverse engineering to determine interaction patterns of the Sequence diagram that can be used by system analysts as a template for designing UML sequence diagrams. Sample applications from android are used as dataset for reverse engineering and pattern identification. The first step is collecting application datasets. The next stage is identifying the features and applications activity, reverse engineering to obtain a sequence diagram model, and then synthesize all of the models into an interaction pattern of sequence diagram. The final step is to test the patterns by implementing it in an application development case stud. The evaluation results concludes that interaction patterns of sequence diagram designs obtained in reverse engineering steps is able to be implemented in software development that contained similar features with the obtained features in this research.

Synthetic biology meets tissue engineering.

Science.gov (United States)

Davies, Jamie A; Cachat, Elise

2016-06-15

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

Engineering and Biology: Counsel for a Continued Relationship

Science.gov (United States)

Levy, Arnon; Siegal, Mark L.; Soyer, Orkun S.; Wagner, Andreas

2015-01-01

Biologists frequently draw on ideas and terminology from engineering. Evolutionary systems biology—with its circuits, switches, and signal processing—is no exception. In parallel with the frequent links drawn between biology and engineering, there is ongoing criticism against this cross-fertilization, using the argument that over-simplistic metaphors from engineering are likely to mislead us as engineering is fundamentally different from biology. In this article, we clarify and reconfigure the link between biology and engineering, presenting it in a more favorable light. We do so by, first, arguing that critics operate with a narrow and incorrect notion of how engineering actually works, and of what the reliance on ideas from engineering entails. Second, we diagnose and diffuse one significant source of concern about appeals to engineering, namely that they are inherently and problematically metaphorical. We suggest that there is plenty of fertile ground left for a continued, healthy relationship between engineering and biology. PMID:26085824

Threshold-Dependent Camouflaged Cells to Secure Circuits Against Reverse Engineering Attacks

OpenAIRE

Collantes, Maria I. Mera; Massad, Mohamed El; Garg, Siddharth

2016-01-01

With current tools and technology, someone who has physical access to a chip can extract the detailed layout of the integrated circuit (IC). By using advanced visual imaging techniques, reverse engineering can reveal details that are meant to be kept secret, such as a secure protocol or novel implementation that offers a competitive advantage. A promising solution to defend against reverse engineering attacks is IC camouflaging. In this work, we propose a new camouflaging technique based on t...

A Survey of Automatic Protocol Reverse Engineering Approaches, Methods, and Tools on the Inputs and Outputs View

Directory of Open Access Journals (Sweden)

Baraka D. Sija

2018-01-01

Full Text Available A network protocol defines rules that control communications between two or more machines on the Internet, whereas Automatic Protocol Reverse Engineering (APRE defines the way of extracting the structure of a network protocol without accessing its specifications. Enough knowledge on undocumented protocols is essential for security purposes, network policy implementation, and management of network resources. This paper reviews and analyzes a total of 39 approaches, methods, and tools towards Protocol Reverse Engineering (PRE and classifies them into four divisions, approaches that reverse engineer protocol finite state machines, protocol formats, and both protocol finite state machines and protocol formats to approaches that focus directly on neither reverse engineering protocol formats nor protocol finite state machines. The efficiency of all approaches’ outputs based on their selected inputs is analyzed in general along with appropriate reverse engineering inputs format. Additionally, we present discussion and extended classification in terms of automated to manual approaches, known and novel categories of reverse engineered protocols, and a literature of reverse engineered protocols in relation to the seven layers’ OSI (Open Systems Interconnection model.

Synthetic biology and its alternatives. Descartes, Kant and the idea of engineering biological machines.

Science.gov (United States)

Kogge, Werner; Richter, Michael

2013-06-01

The engineering-based approach of synthetic biology is characterized by an assumption that 'engineering by design' enables the construction of 'living machines'. These 'machines', as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes's and Kant's thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology's engineering paradigm. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reverse Engineering Integrated Circuits Using Finite State Machine Analysis

Energy Technology Data Exchange (ETDEWEB)

Oler, Kiri J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Miller, Carl H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2016-04-12

In this paper, we present a methodology for reverse engineering integrated circuits, including a mathematical verification of a scalable algorithm used to generate minimal finite state machine representations of integrated circuits.

A Process Re-engineering Framework for Reverse Logistics based on a Case Study

Directory of Open Access Journals (Sweden)

Hing Kai Chan

2010-09-01

Full Text Available Reverse logistics has gained increasing attention in recent years as a channel for companies to achieve operational excellence. The process involves manipulation of returned materials, or even products, which forms a pivotal role in sustainable development throughout the whole supply chains. To make reverse logistics possible, process re-engineering may need to be carried out. However, the processes involved in reengineering are practically complicated. Objectives, benefits, and applicability of any process re-engineering require a careful and detailed strategic planning. This paper aims to propose an easy-to-follow step-by-step framework for practitioners to perform process re-engineering, to learn and identify the critical issues in each step, and to be successful in applying process re-engineering in order to enhance reverse logistics performance. A learner-centred approach is adopted based on a case study of process re-engineering, which is demonstrated in the paper for explanation.

Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

Science.gov (United States)

Chen, Bor-Sen; Wu, Chia-Chou

2013-01-01

Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

Directory of Open Access Journals (Sweden)

Bor-Sen Chen

2013-10-01

Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

An engineering design approach to systems biology.

Science.gov (United States)

Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

2017-07-17

Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

Mobile Timekeeping Application Built on Reverse-Engineered JPL Infrastructure

Science.gov (United States)

Witoff, Robert J.

2013-01-01

Every year, non-exempt employees cumulatively waste over one man-year tracking their time and using the timekeeping Web page to save those times. This app eliminates this waste. The innovation is a native iPhone app. Libraries were built around a reverse- engineered JPL API. It represents a punch-in/punch-out paradigm for timekeeping. It is accessible natively via iPhones, and features ease of access. Any non-exempt employee can natively punch in and out, as well as save and view their JPL timecard. This app is built on custom libraries created by reverse-engineering the standard timekeeping application. Communication is through custom libraries that re-route traffic through BrowserRAS (remote access service). This has value at any center where employees track their time.

Biology: An Important Agricultural Engineering Mechanism

Science.gov (United States)

Henderson, S. M.

1974-01-01

Describes the field of bioengineering with particular emphasis on agricultural engineering, and presents the results of a survey of schools that combine biology and engineering in their curricula. (JR)

Synthetic Biology to Engineer Bacteriophage Genomes.

Science.gov (United States)

Rita Costa, Ana; Milho, Catarina; Azeredo, Joana; Pires, Diana Priscila

2018-01-01

Recent advances in the synthetic biology field have enabled the development of new molecular biology techniques used to build specialized bacteriophages with new functionalities. Bacteriophages have been engineered towards a wide range of applications including pathogen control and detection, targeted drug delivery, or even assembly of new materials.In this chapter, two strategies that have been successfully used to genetically engineer bacteriophage genomes are addressed: a yeast-based platform and bacteriophage recombineering of electroporated DNA.

RegnANN: Reverse Engineering Gene Networks using Artificial Neural Networks.

Directory of Open Access Journals (Sweden)

Marco Grimaldi

Full Text Available RegnANN is a novel method for reverse engineering gene networks based on an ensemble of multilayer perceptrons. The algorithm builds a regressor for each gene in the network, estimating its neighborhood independently. The overall network is obtained by joining all the neighborhoods. RegnANN makes no assumptions about the nature of the relationships between the variables, potentially capturing high-order and non linear dependencies between expression patterns. The evaluation focuses on synthetic data mimicking plausible submodules of larger networks and on biological data consisting of submodules of Escherichia coli. We consider Barabasi and Erdös-Rényi topologies together with two methods for data generation. We verify the effect of factors such as network size and amount of data to the accuracy of the inference algorithm. The accuracy scores obtained with RegnANN is methodically compared with the performance of three reference algorithms: ARACNE, CLR and KELLER. Our evaluation indicates that RegnANN compares favorably with the inference methods tested. The robustness of RegnANN, its ability to discover second order correlations and the agreement between results obtained with this new methods on both synthetic and biological data are promising and they stimulate its application to a wider range of problems.

Biological aspects of tissue-engineered cartilage.

Science.gov (United States)

Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

2018-04-01

Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

‘Can Simple Biological Systems be Built from Standardized Interchangeable Parts?’:Negotiating Biology and Engineering in a Synthetic Biology Competition

OpenAIRE

Frow, Emma; Calvert, Jane

2013-01-01

Synthetic biology represents a recent attempt to bring engineering principles and practices to working with biology. In practice, the nature of the relationship between engineering and biology in synthetic biology is a subject of ongoing debate. The disciplines of biology and engineering are typically seen to involve differentways of knowing and doing, and to embody different assumptions and objectives. Tensions between these approaches are playing out as the field of synthetic biology is bei...

Teach CAD and Measuring Skills through Reverse Engineering

Science.gov (United States)

Board, Keith

2012-01-01

This article describes a reverse engineering activity that gives students hands-on, minds-on experience with measuring tools, machine parts, and CAD. The author developed this activity to give students an abundance of practical experience with measuring tools. Equally important, it provides a good interface between the virtual world of CAD 3D…

IntegromeDB: an integrated system and biological search engine.

Science.gov (United States)

Baitaluk, Michael; Kozhenkov, Sergey; Dubinina, Yulia; Ponomarenko, Julia

2012-01-19

With the growth of biological data in volume and heterogeneity, web search engines become key tools for researchers. However, general-purpose search engines are not specialized for the search of biological data. Here, we present an approach at developing a biological web search engine based on the Semantic Web technologies and demonstrate its implementation for retrieving gene- and protein-centered knowledge. The engine is available at http://www.integromedb.org. The IntegromeDB search engine allows scanning data on gene regulation, gene expression, protein-protein interactions, pathways, metagenomics, mutations, diseases, and other gene- and protein-related data that are automatically retrieved from publicly available databases and web pages using biological ontologies. To perfect the resource design and usability, we welcome and encourage community feedback.

International Conference on Medical and Biological Engineering 2017

CERN Document Server

2017-01-01

This volume presents the proceedings of the International Conference on Medical and Biological Engineering held from 16 to 18 March 2017 in Sarajevo, Bosnia and Herzegovina. Focusing on the theme of ‘Pursuing innovation. Shaping the future’, it highlights the latest advancements in Biomedical Engineering and also presents the latest findings, innovative solutions and emerging challenges in this field. Topics include: - Biomedical Signal Processing - Biomedical Imaging and Image Processing - Biosensors and Bioinstrumentation - Bio-Micro/Nano Technologies - Biomaterials - Biomechanics, Robotics and Minimally Invasive Surgery - Cardiovascular, Respiratory and Endocrine Systems Engineering - Neural and Rehabilitation Engineering - Molecular, Cellular and Tissue Engineering - Bioinformatics and Computational Biology - Clinical Engineering and Health Technology Assessment - Health Informatics, E-Health and Telemedicine - Biomedical Engineering Education - Pharmaceutical Engineering.

Biological Systems Thinking for Control Engineering Design

Directory of Open Access Journals (Sweden)

D. J. Murray-Smith

2004-01-01

Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

Science.gov (United States)

Floares, Alexandru George

2008-01-01

Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

Understanding Virtual Objects through Reverse Engineering

Directory of Open Access Journals (Sweden)

Vera Moitinho

2012-11-01

Full Text Available The main objective of our research is to develop a new methodology, based on Reverse Engineering processes – 3D scan, quantitative data analysis and Artificial Intelligence techniques, in particular simulation – to study the relationship between form and function of artefacts. Furthermore, we aim to provide new data, as well as possible explanations of the archaeological record according to what it expects about social activity, including working processes, by simulating the potentialities of such actions in terms of input-output relationships.

Drag reduction of a reverse-engineered vehicle

Energy Technology Data Exchange (ETDEWEB)

Lecrivain, G.; Slaouti, A.; Kennedy, I. [Manchester Metropolitan Univ., Manchester (United Kingdom). Dept. of Engineering and Technology

2007-08-09

The aerodynamic performance of a hand-made sports car was numerically assessed using computational fluid dynamics (CFD) analysis of various shape modifications. The purpose was to achieve a lower drag design. Reverse-engineering was used to create a virtual model of complex 3D shapes for which no computer-aided drawings (CAD) data existed. From the predicted flow, the body could be redesigned for better performance prior to its remanufacturing. This paper described the multidisciplinary procedure involving reverse-engineering and CAD that was used to recreate a suitable watertight model of the sports car. The different errors embedded in the successive stages leading to the final model were accurately assessed and minimized. The whole vehicle was remodelled for drag reduction. Surface reconstruction was carried out, an an accurate set of high quality Non-Uniform Rational B-Spline (NURBS) surfaces was produced over the polygonal mesh resulting in a fine visual surface finish with smooth lines and contours, as required in the automotive industry. Further modifications were implemented for the purpose of drag reduction and to improve its aerodynamic performance. The application described in this paper can be extended to any other similarly intricate vehicle or industrial component. 12 refs., 1 tab., 11 figs.

Variable Cycle Intake for Reverse Core Engine

Science.gov (United States)

Suciu, Gabriel L (Inventor); Chandler, Jesse M (Inventor); Staubach, Joseph B (Inventor)

2016-01-01

A gas generator for a reverse core engine propulsion system has a variable cycle intake for the gas generator, which variable cycle intake includes a duct system. The duct system is configured for being selectively disposed in a first position and a second position, wherein free stream air is fed to the gas generator when in the first position, and fan stream air is fed to the gas generator when in the second position.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

Science.gov (United States)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Basic science through engineering? Synthetic modeling and the idea of biology-inspired engineering.

Science.gov (United States)

Knuuttila, Tarja; Loettgers, Andrea

2013-06-01

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more "biology inspired." Copyright © 2013 Elsevier Ltd. All rights reserved.

The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

Science.gov (United States)

Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

2012-01-01

Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

Parametric Optimization Design of Brake Block Based on Reverse Engineering

Directory of Open Access Journals (Sweden)

Jin Hua-wei

2017-01-01

Full Text Available As one of the key part of automotive brake,the performance of brake block has a direct impact on the safety and comfort of cars. Modeling the brake block of disc brake in reverse parameterization by reverse engineering software, analyzing and optimizing the reconstructed model by CAE software. Processing the scanned point cloud by Geomagic Studio and reconstructing the CAD model of the brake block with the parametric surface function of the software, then analyzing and optimizing it by Wrokbench. The example shows that it is quick to reconstruct the CAD model of parts by using reverse parameterization method and reduce part re-design development cycle significantly.

High Pressure Reverse Flow APS Engine

Science.gov (United States)

Senneff, J. M.

1972-01-01

A design and test demonstration effort was undertaken to evaluate the concept of the reverse flow engine for the APS engine application. The 1500 lb (6672 N) thrust engine was designed to operate on gaseous hydrogen and gaseous oxygen propellants at a mixture ratio of 4 and to achieve the objective performance of 435 sec (4266 Nsec/kg) specific impulse. Superimposed durability requirements called for a million-cycle capability with 50 hours duration. The program was undertaken as a series of tasks including the initial preliminary design, design of critical test components and finally, the design and demonstration of an altitude engine which could be used interchangeably to examine operating parameters as well as to demonstrate the capability of the concept. The program results are reported with data to indicate that all of the program objectives were met or exceeded within the course of testing on the program. The analysis effort undertaken is also reported in detail and supplemented with test data in some cases where prior definitions could not be made. The results are contained of these analyses as well as the test results conducted throughout the course of the program. Finally, the test data and analytical results were combined to allow recommendations for a flight weight design. This preliminary design effort is also detailed.

Advancing metabolic engineering through systems biology of industrial microorganisms

DEFF Research Database (Denmark)

Dai, Zongjie; Nielsen, Jens

2015-01-01

resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review......Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further....

Novel combination of reverse engineering and vapid prototyping in medicine

CSIR Research Space (South Africa)

Schenker, R

1999-08-01

Full Text Available The technologies of reverse engineering and rapid prototyping are emerging as useful new tools in medicine. One application is of particular interest in orthopaedic, dental and reconstructive surgery. It involves the imaging, modelling...

Engineering a Biological Revolution.

Science.gov (United States)

Matheson, Susan

2017-01-26

The new field of synthetic biology promises to change health care, computer technology, the production of biofuels, and more. Students participating in the International Genetically Engineered Machine (iGEM) competition are on the front lines of this revolution. Copyright © 2017 Elsevier Inc. All rights reserved.

Reverse Ecology: from systems to environments and back.

Science.gov (United States)

Levy, Roie; Borenstein, Elhanan

2012-01-01

The structure of complex biological systems reflects not only their function but also the environments in which they evolved and are adapted to. Reverse Ecology-an emerging new frontier in Evolutionary Systems Biology-aims to extract this information and to obtain novel insights into an organism's ecology. The Reverse Ecology framework facilitates the translation of high-throughput genomic data into large-scale ecological data, and has the potential to transform ecology into a high-throughput field. In this chapter, we describe some of the pioneering work in Reverse Ecology, demonstrating how system-level analysis of complex biological networks can be used to predict the natural habitats of poorly characterized microbial species, their interactions with other species, and universal patterns governing the adaptation of organisms to their environments. We further present several studies that applied Reverse Ecology to elucidate various aspects of microbial ecology, and lay out exciting future directions and potential future applications in biotechnology, biomedicine, and ecological engineering.

Critical evaluation of reverse engineering tool Imagix 4D!

Science.gov (United States)

Yadav, Rashmi; Patel, Ravindra; Kothari, Abhay

2016-01-01

The comprehension of legacy codes is difficult to understand. Various commercial reengineering tools are available that have unique working styles, and are equipped with their inherent capabilities and shortcomings. The focus of the available tools is in visualizing static behavior not the dynamic one. Therefore, it is difficult for people who work in software product maintenance, code understanding reengineering/reverse engineering. Consequently, the need for a comprehensive reengineering/reverse engineering tool arises. We found the usage of Imagix 4D to be good as it generates the maximum pictorial representations in the form of flow charts, flow graphs, class diagrams, metrics and, to a partial extent, dynamic visualizations. We evaluated Imagix 4D with the help of a case study involving a few samples of source code. The behavior of the tool was analyzed on multiple small codes and a large code gcc C parser. Large code evaluation was performed to uncover dead code, unstructured code, and the effect of not including required files at preprocessing level. The utility of Imagix 4D to prepare decision density and complexity metrics for a large code was found to be useful in getting to know how much reengineering is required. At the outset, Imagix 4D offered limitations in dynamic visualizations, flow chart separation (large code) and parsing loops. The outcome of evaluation will eventually help in upgrading Imagix 4D and posed a need of full featured tools in the area of software reengineering/reverse engineering. It will also help the research community, especially those who are interested in the realm of software reengineering tool building.

Strategies for replacement of obsolete equipment - including reverse engineering

International Nuclear Information System (INIS)

Irish, C.S.

2000-01-01

The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of: commercially available equivalent component; modification of a commercial available component; reverse engineering of the original component; and finally, design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: Missing, misleading or no information on the original component; Acquiring information from the original equipment manufacturer and the plant; Using a sample component for the replacement evaluation and or reverse engineering; and Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

Advancing metabolic engineering through systems biology of industrial microorganisms.

Science.gov (United States)

Dai, Zongjie; Nielsen, Jens

2015-12-01

Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further. Copyright © 2015 Elsevier Ltd. All rights reserved.

Challenges and opportunities in synthetic biology for chemical engineers.

Science.gov (United States)

Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

2013-11-15

Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement.

Reverse Flow Engine Core Having a Ducted Fan with Integrated Secondary Flow Blades

Science.gov (United States)

Kisska, Michael K. (Inventor); Princen, Norman H. (Inventor); Kuehn, Mark S. (Inventor); Cosentino, Gary B. (Inventor)

2014-01-01

Secondary air flow is provided for a ducted fan having a reverse flow turbine engine core driving a fan blisk. The fan blisk incorporates a set of thrust fan blades extending from an outer hub and a set of integral secondary flow blades extending intermediate an inner hub and the outer hub. A nacelle provides an outer flow duct for the thrust fan blades and a secondary flow duct carries flow from the integral secondary flow blades as cooling air for components of the reverse flow turbine engine.

Strategies for replacement of obsolete equipment, including reverse engineering

International Nuclear Information System (INIS)

Irish, C.S.

2003-01-01

The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of, (1) commercially available equivalent component, (2) modification of a commercial available component, (3) reverse engineering of the original component and finally (4) design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: 1) Missing, misleading or no information on the original component. 2) Acquiring information from the original equipment manufacturer and the plant. 3) Using a sample component for the replacement evaluation and or reverse engineering. 4) Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

Challenges and opportunities in synthetic biology for chemical engineers

Science.gov (United States)

Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

2012-01-01

Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. PMID:24222925

Synthetic Biology: Engineering Living Systems from Biophysical Principles.

Science.gov (United States)

Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

2017-03-28

Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Synthetic biology approaches to engineer T cells.

Science.gov (United States)

Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

2015-08-01

There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reversible S-nitrosylation in an engineered azurin

Energy Technology Data Exchange (ETDEWEB)

Tian, Shiliang; Liu, Jing; Cowley, Ryan E.; Hosseinzadeh, Parisa; Marshall, Nicholas M.; Yu, Yang; Robinson, Howard; Nilges, Mark J.; Blackburn, Ninian J.; Solomon, Edward I.; Lu, Yi

2016-04-25

S-Nitrosothiols are known as reagents for NO storage and transportation and as regulators in many physiological processes. Although the S-nitrosylation catalysed by haem proteins is well known, no direct evidence of S-nitrosylation in copper proteins has been reported. Here, we report reversible insertion of NO into a copper–thiolate bond in an engineered copper centre in Pseudomonas aeruginosa azurin by rational design of the primary coordination sphere and tuning its reduction potential by deleting a hydrogen bond in the secondary coordination sphere. The results not only provide the first direct evidence of S-nitrosylation of Cu(II)-bound cysteine in metalloproteins, but also shed light on the reaction mechanism and structural features responsible for stabilizing the elusive Cu(I)–S(Cys)NO species. The fast, efficient and reversible S-nitrosylation reaction is used to demonstrate its ability to prevent NO inhibition of cytochrome bo3 oxidase activity by competing for NO binding with the native enzyme under physiologically relevant conditions.

Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.

Science.gov (United States)

De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

2013-01-01

Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.

Synthetic biology: engineering molecular computers

CERN Multimedia

CERN. Geneva

2018-01-01

Complicated systems cannot survive the rigors of a chaotic environment, without balancing mechanisms that sense, decide upon and counteract the exerted disturbances. Especially so with living organisms, forced by competition to incredible complexities, escalating also their self-controlling plight. Therefore, they compute. Can we harness biological mechanisms to create artificial computing systems? Biology offers several levels of design abstraction: molecular machines, cells, organisms... ranging from the more easily-defined to the more inherently complex. At the bottom of this stack we find the nucleic acids, RNA and DNA, with their digital structure and relatively precise interactions. They are central enablers of designing artificial biological systems, in the confluence of engineering and biology, that we call Synthetic biology. In the first part, let us follow their trail towards an overview of building computing machines with molecules -- and in the second part, take the case study of iGEM Greece 201...

Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

Science.gov (United States)

He, Fei; Murabito, Ettore; Westerhoff, Hans V

2016-04-01

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

Transcription control engineering and applications in synthetic biology

Directory of Open Access Journals (Sweden)

Michael D. Engstrom

2017-09-01

Full Text Available In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein, a.k.a. gene regulation. Regulation is critical for optimizing protein (and therefore activity levels and the subsequent levels of metabolites and other cellular properties. The central dogma of molecular biology posits that information flow commences with transcription, and accordingly, regulatory tools targeting transcription have received the most attention in synthetic biology. In this mini-review, we highlight many past successes and summarize the lessons learned in developing tools for controlling transcription. In particular, we focus on engineering studies where promoters and transcription terminators (cis-factors were directly engineered and/or isolated from DNA libraries. We also review several well-characterized transcription regulators (trans-factors, giving examples of how cis- and trans-acting factors have been combined to create digital and analogue switches for regulating transcription in response to various signals. Last, we provide examples of how engineered transcription control systems have been used in metabolic engineering and more complicated genetic circuits. While most of our mini-review focuses on the well-characterized bacterium Escherichia coli, we also provide several examples of the use of transcription control engineering in non-model organisms. Similar approaches have been applied outside the bacterial kingdom indicating that the lessons learned from bacterial studies may be generalized for other organisms.

Transcription control engineering and applications in synthetic biology.

Science.gov (United States)

Engstrom, Michael D; Pfleger, Brian F

2017-09-01

In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein), a.k.a. gene regulation. Regulation is critical for optimizing protein (and therefore activity) levels and the subsequent levels of metabolites and other cellular properties. The central dogma of molecular biology posits that information flow commences with transcription, and accordingly, regulatory tools targeting transcription have received the most attention in synthetic biology. In this mini-review, we highlight many past successes and summarize the lessons learned in developing tools for controlling transcription. In particular, we focus on engineering studies where promoters and transcription terminators ( cis -factors) were directly engineered and/or isolated from DNA libraries. We also review several well-characterized transcription regulators ( trans- factors), giving examples of how cis- and trans -acting factors have been combined to create digital and analogue switches for regulating transcription in response to various signals. Last, we provide examples of how engineered transcription control systems have been used in metabolic engineering and more complicated genetic circuits. While most of our mini-review focuses on the well-characterized bacterium Escherichia coli , we also provide several examples of the use of transcription control engineering in non-model organisms. Similar approaches have been applied outside the bacterial kingdom indicating that the lessons learned from bacterial studies may be generalized for other organisms.

Experimental and modelling study of reverse flow catalytic converters for natural gas/diesel dual fuel engine pollution control

Energy Technology Data Exchange (ETDEWEB)

Liu, B.

2000-07-01

There is renewed interest in the development of natural gas vehicles in response to the challenge to reduce urban air pollution and consumption of petroleum. The natural gas/diesel dual fuel engine is one way to apply natural gas to the conventional diesel engine. Dual fuel engines operating on natural gas and diesel emit less nitrogen oxides, and less carbon soot to the air compared to conventional diesel engines. The problem is that at light loads, fuel efficiency is reduced and emissions of hydrocarbons and carbon monoxide are increased. This thesis focused on control methods for emissions of hydrocarbons and carbon monoxide in the dual fuel engine at light loads. This was done by developing a reverse flow catalytic converter to complement dual fuel engine exhaust characteristics. Experimental measurements and numerical simulations of reverse flow catalytic converters were conducted. Reverse flow creates a high reactor temperature even when the engine is run at low exhaust temperature levels at light loads. The increase in reactor temperature from reverse flow could be 2 or 3 times higher than the adiabatic temperature increase, which is based on the reactor inlet temperature and concentration. This temperature makes it possible for greater than 90 per cent of the hydrocarbon and carbon monoxide to be converted with a palladium based catalyst. Reverse flow appears to be better than conventional unidirectional flow to deal with natural gas/diesel dual fuel engine pollution at light loads. Reverse flow could also maintain reactor temperature at over 800 K and hydrocarbon conversion at about 80 per cent during testing. The newly presented model simulates reactor performance with reasonable accuracy. Both carbon monoxide and methane oxidation over the palladium catalyst in excess oxygen and water were described using first order kinetics.

Understanding and Enhancing Soil Biological Health: The Solution for Reversing Soil Degradation

Directory of Open Access Journals (Sweden)

R. Michael Lehman

2015-01-01

Full Text Available Our objective is to provide an optimistic strategy for reversing soil degradation by increasing public and private research efforts to understand the role of soil biology, particularly microbiology, on the health of our world’s soils. We begin by defining soil quality/soil health (which we consider to be interchangeable terms, characterizing healthy soil resources, and relating the significance of soil health to agroecosystems and their functions. We examine how soil biology influences soil health and how biological properties and processes contribute to sustainability of agriculture and ecosystem services. We continue by examining what can be done to manipulate soil biology to: (i increase nutrient availability for production of high yielding, high quality crops; (ii protect crops from pests, pathogens, weeds; and (iii manage other factors limiting production, provision of ecosystem services, and resilience to stresses like droughts. Next we look to the future by asking what needs to be known about soil biology that is not currently recognized or fully understood and how these needs could be addressed using emerging research tools. We conclude, based on our perceptions of how new knowledge regarding soil biology will help make agriculture more sustainable and productive, by recommending research emphases that should receive first priority through enhanced public and private research in order to reverse the trajectory toward global soil degradation.

Mammalian Synthetic Biology: Engineering Biological Systems.

Science.gov (United States)

Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

2017-06-21

The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

[Are there pseudophototropic reactions in biology? Part 4: On the reversibility of biologic/synthetic polymere systems (author's transl)].

Science.gov (United States)

Patschorke, J

1979-01-01

In further research on pseudophototropic behaviour in cellular membranes of halobacteria the reversibility of vinylmethylethermaleic anhydride-copolymeres with biological liquids is tested and the basic principles of different colour generating reactions are studied.

Adding Robustness to Support Vector Machines Against Adversarial Reverse Engineering

KAUST Repository

Alabdulmohsin, Ibrahim

2014-01-01

Many classification algorithms have been successfully deployed in security-sensitive applications including spam filters and intrusion detection systems. Under such adversarial environments, adversaries can generate exploratory attacks against the defender such as evasion and reverse engineering. In this paper, we discuss why reverse engineering attacks can be carried out quite efficiently against fixed classifiers, and investigate the use of randomization as a suitable strategy for mitigating their risk. In particular, we derive a semidefinite programming (SDP) formulation for learning a distribution of classifiers subject to the constraint that any single classifier picked at random from such distribution provides reliable predictions with a high probability. We analyze the tradeoff between variance of the distribution and its predictive accuracy, and establish that one can almost always incorporate randomization with large variance without incurring a loss in accuracy. In other words, the conventional approach of using a fixed classifier in adversarial environments is generally Pareto suboptimal. Finally, we validate such conclusions on both synthetic and real-world classification problems. Copyright 2014 ACM.

Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

Science.gov (United States)

Wen, Shameng; Meng, Qingkun; Feng, Chao; Tang, Chaojing

2017-01-01

Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

Introduction to bioengineering: melding of engineering and biological sciences.

Science.gov (United States)

Shoureshi, Rahmat A

2005-04-01

Engineering has traditionally focused on the external extensions of organisms, such as transportation systems, high-rise buildings, and entertainment systems. In contrast, bioengineering is concerned with inward processes of biologic organisms. Utilization of engineering principles and techniques in the analysis and solution of problems in medicine and biology is the basis for bioengineering. This article discusses subspecialties in bioengineering and presents examples of projects in this discipline.

Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

Science.gov (United States)

Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

1998-01-01

Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

Science.gov (United States)

Ganguli, Suman; Hunt, C Anthony

2004-01-01

Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

Neutron tomography as a reverse engineering method applied to the IS-60 Rover gas turbine

CSIR Research Space (South Africa)

Roos, TH

2011-09-01

Full Text Available Probably the most common method of reverse engineering in mechanical engineering involves measuring the physical geometry of a component using a coordinate measuring machine (CMM). Neutron tomography, in contrast, is used primarily as a non...

Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Nielsen, Jens; Jewett, Michael Christopher

2008-01-01

in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

Directory of Open Access Journals (Sweden)

Shameng Wen

Full Text Available Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

[Reconstruction and measurement of a digital dental model using grating projection and reverse engineering].

Science.gov (United States)

Zhenzhen, Wang; Yi, Lu; Jun, Song; Jun, Chen; Qin, Zhou

2015-02-01

This work lays the foundation for establishing a digital model database with normal occlusion. A digital dental cast is acquired through grating projection, and model features are measured through reverse engineering. The grating projection system controlled by a computer was projected onto the surface of a normal dental model. Three-dimensional contour data were obtained through multi-angle shooting. A three-dimensional model was constructed, and the model features were analyzed by using reverse engineering. The digital model was compared with the plaster model to determine the accuracy of the measurement system. The structure of three-dimensional reconstruction model was clear. The digital models of two measurements exhibited no significant difference (P > 0.05). When digital and plaster models were measured, we found that the crown length and arch width were not statistically different (P > 0.05), whereas the difference between the crown width and arch length was statistically significant (P model by using the grating projection technique and reverse engineering can be used for dental model measurement in clinic al and scientific research and can provide a scientific method for establishing a digital model database with normal occlusion.

Reverse engineering of a railcar prototype via energetic macroscopic representation approach

International Nuclear Information System (INIS)

Agbli, Kréhi Serge; Hissel, Daniel; Sorrentino, Marco; Chauvet, Frédéric; Pouget, Julien

2016-01-01

Highlights: • A complex EMR model of a new railcar range has been developed. • A satisfactory assessment of the fuel consumption of the railcar. • The significant potential benefits are attainable by hybridizing the original railcar. • The regenerative braking can provide up to 240 kW h saving. - Abstract: Energetic Macroscopic Representation (EMR) modelling approach is proposed to perform model-based reverse-engineering of a new railcar range, having six propulsion units, each consisting of a diesel engine and a traction motor. Particularly, EMR intrinsic features were exploited to perform phenomenological structuration of power flows, thus allowing proper and comprehensive modelling of complex systems, such as the under-study railcar. Based on some prospective real trips, selected in such a way as to enable realistic evaluation of effective railcar effort, EMR-based prediction of railcar energy consumption is performed. Furthermore, physical consistency of each powertrain component operation was carefully verified. The suitability of EMR approach was thus proven effective to perform reverse-engineering of known specifications and available experimental data, with the final aim of reconstructing a high fidelity computational tool that meets computational burden requirements for subsequent model-based tasks deployment. Finally, specific simulation analyses were performed to evaluate the potential benefits attainable through electric hybridization of the original powertrain.

Comparing Two Definitions of Work for a Biological Quantum Heat Engine

International Nuclear Information System (INIS)

Xu You-Yang; Zhao Shun-Cai; Liu Juan

2015-01-01

Systems of photosynthetic reaction centres have been modelled as heat engines, while it has also been reported that the efficiency and power of such heat engines can be enhanced by quantum interference — a trait that has attracted much interest. We compare two definitions of the work of such a photosynthetic heat engine, i.e. definition A used by Weimer et al. and B by Dorfman et al. We also introduce a coherent interaction between donor and acceptor (CIDA) to demonstrate a reversible energy transport. We show that these two definitions of work can impart contradictory results, that is, CIDA enhances the power and efficiency of the photosynthetic heat engine with definition B but not with A. Additionally, we find that both reversible and irreversible excitation-energy transport can be described with definition A, but definition B can only model irreversible transport. As a result, we conclude that definition A is more suitable for photosynthetic systems than definition B. (paper)

Biological augmentation and tissue engineering approaches in meniscus surgery.

Science.gov (United States)

Moran, Cathal J; Busilacchi, Alberto; Lee, Cassandra A; Athanasiou, Kyriacos A; Verdonk, Peter C

2015-05-01

The purpose of this review was to evaluate the role of biological augmentation and tissue engineering strategies in meniscus surgery. Although clinical (human), preclinical (animal), and in vitro tissue engineering studies are included here, we have placed additional focus on addressing preclinical and clinical studies reported during the 5-year period used in this review in a systematic fashion while also providing a summary review of some important in vitro tissue engineering findings in the field over the past decade. A search was performed on PubMed for original works published from 2009 to March 31, 2014 using the term "meniscus" with all the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were the following: English-language articles and original clinical, preclinical (in vivo), and in vitro studies of tissue engineering and regenerative medicine application in knee meniscus lesions published from 2009 to March 31, 2014. Three clinical studies and 18 preclinical studies were identified along with 68 tissue engineering in vitro studies. These reports show the increasing promise of biological augmentation and tissue engineering strategies in meniscus surgery. The role of stem cell and growth factor therapy appears to be particularly useful. A review of in vitro tissue engineering studies found a large number of scaffold types to be of promise for meniscus replacement. Limitations include a relatively low number of clinical or preclinical in vivo studies, in addition to the fact there is as yet no report in the literature of a tissue-engineered meniscus construct used clinically. Neither does the literature provide clarity on the optimal meniscus scaffold type or biological augmentation with which meniscus repair or replacement would be best addressed in the future. There is increasing focus on the role of mechanobiology and biomechanical and

1st Global Conference on Biomedical Engineering & 9th Asian-Pacific Conference on Medical and Biological Engineering

CERN Document Server

Wang, Shyh-Hau; Yeh, Ming-Long

2015-01-01

This volume presents the proceedings of the 9th Asian-Pacific Conference on Medical and Biological Engineering (APCMBE 2014). The proceedings address a broad spectrum of topics from Bioengineering and Biomedicine, like Biomaterials, Artificial Organs, Tissue Engineering, Nanobiotechnology and Nanomedicine, Biomedical Imaging, Bio MEMS, Biosignal Processing, Digital Medicine, BME Education. It helps medical and biological engineering professionals to interact and exchange their ideas and experiences.

Challenges of medical and biological engineering and science

Energy Technology Data Exchange (ETDEWEB)

Magjarevic, R [University of Zagreb, Faculty of Electrical Engineering and Computing, Zagreb (Croatia)

2004-07-01

All aspects of biomedical engineering and science, from research and development, education and training, implementation in health care systems, internationalisation and globalisation, and other, new issues are present in the strategy and in action plans of the International Federation for Medical and Biological Engineering (IFMBE) which, with help of a large number of highly motivated volunteers, will stay in leading position in biomedical engineering and science.

Challenges of medical and biological engineering and science

International Nuclear Information System (INIS)

Magjarevic, R.

2004-01-01

All aspects of biomedical engineering and science, from research and development, education and training, implementation in health care systems, internationalisation and globalisation, and other, new issues are present in the strategy and in action plans of the International Federation for Medical and Biological Engineering (IFMBE) which, with help of a large number of highly motivated volunteers, will stay in leading position in biomedical engineering and science

Experiential Engineering through iGEM--An Undergraduate Summer Competition in Synthetic Biology

Science.gov (United States)

Mitchell, Rudolph; Dori, Yehudit Judy; Kuldell, Natalie H.

2011-01-01

Unlike students in other engineering disciplines, undergraduates in biological engineering typically have limited opportunity to develop design competencies, and even fewer chances to implement their designed projects. The international Genetically Engineered Machines (iGEM) competition is a student Synthetic Biology competition that, in 2009,…

Biometrics in wearable products: Reverse Engineering and numerical modeling

OpenAIRE

Rao, Andrea

2011-01-01

The Reverse Engineering (RE) techniques and the Finite Element Modelling (FEM) are widely used tools in many scientific fields. They were firstly developed for the mechanics but in the last times became common for other disciplines. In the thesis these techniques are used for the customization of the wearable products. It is possible to observe that the geometry of whatever wearable product is fundamental for the comfort. In particular, starting from the need of wearable product it is possibl...

Future of Chemical Engineering: Integrating Biology into the Undergraduate ChE Curriculum

Science.gov (United States)

Mosto, Patricia; Savelski, Mariano; Farrell, Stephanie H.; Hecht, Gregory B.

2007-01-01

Integrating biology in the chemical engineering curriculum seems to be the future for chemical engineering programs nation and worldwide. Rowan University's efforts to address this need include a unique chemical engineering curriculum with an intensive biology component integrated throughout from freshman to senior years. Freshman and Sophomore…

Flight Measurements of the Effect of a Controllable Thrust Reverser on the Flight Characteristics of a Single-Engine Jet Airplane

Science.gov (United States)

Anderson, Seth B.; Cooper, George E.; Faye, Alan E., Jr.

1959-01-01

A flight investigation was undertaken to determine the effect of a fully controllable thrust reverser on the flight characteristics of a single-engine jet airplane. Tests were made using a cylindrical target-type reverser actuated by a hydraulic cylinder through a "beep-type" cockpit control mounted at the base of the throttle. The thrust reverser was evaluated as an in-flight decelerating device, as a flight path control and airspeed control in landing approach, and as a braking device during the ground roll. Full deflection of the reverser for one reverser configuration resulted in a reverse thrust ratio of as much as 85 percent, which at maximum engine power corresponded to a reversed thrust of 5100 pounds. Use of the reverser in landing approach made possible a wide selection of approach angles, a large reduction in approach speed at steep approach angles, improved control of flight path angle, and more accuracy in hitting a given touchdown point. The use of the reverser as a speed brake at lower airspeeds was compromised by a longitudinal trim change. At the lower airspeeds and higher engine powers there was insufficient elevator power to overcome the nose-down trim change at full reverser deflection.

Interactive scalable condensation of reverse engineered UML class diagrams for software comprehension

NARCIS (Netherlands)

Osman, Mohd Hafeez Bin

2015-01-01

Software design documentation is a valuable aid in software comprehension. However, keeping the software design up-to-date with evolving source code is challenging and time-consuming. Reverse engineering is one of the options for recovering software architecture from the implementation code.

Update of GRASP/Ada reverse engineering tools for Ada

Science.gov (United States)

Cross, James H., II

1993-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional pretty printed Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype CSD generator (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3,e two update phases were completed. Update'92 focused on the initial analysis of evaluation data collected from software engineering students at Auburn University and the addition of significant enhancements to the user interface. Update'93 (the current update) focused on the statistical analysis of the data collected in the previous update and preparation of Version 3.4 of the prototype for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical

GRASP/Ada 95: Reverse Engineering Tools for Ada

Science.gov (United States)

Cross, James H., II

1996-01-01

The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped an algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD), and a new visualization for a fine-grained complexity metric called the Complexity Profile Graph (CPG). By synchronizing the CSD and the CPG, the CSD view of control structure, nesting, and source code is directly linked to the corresponding visualization of statement level complexity in the CPG. GRASP has been integrated with GNAT, the GNU Ada 95 Translator to provide a comprehensive graphical user interface and development environment for Ada 95. The user may view, edit, print, and compile source code as a CSD with no discernible addition to storage or computational overhead. The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada 95 source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. The current update has focused on the design and implementation of a new Motif compliant user interface, and a new CSD generator consisting of a tagger and renderer. The Complexity Profile Graph (CPG) is based on a set of functions that describes the context, content, and the scaling for complexity on a statement by statement basis. When combined graphicafly, the result is a composite profile of complexity for the program unit. Ongoing research includes the development and refinement of the associated functions, and the development of the CPG generator prototype. The current Version 5.0 prototype provides the capability for the user to generate CSDs and CPGs from Ada 95 source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for

An Application of Reverse Engineering in Design of the Spur Gear

Directory of Open Access Journals (Sweden)

Adem Çiçek

2010-06-01

Full Text Available In this study, it is aimed that the gear parameters required the design of a spur gear are obtained by use of reverse engineering techniques. Therefore, point cloud of tooth profile of the manufactured spur gear is extracted by a coordinate measuring machine (CMM. The gear parameters are derived by processing the obtained point cloud. 3D model of the spur gear are modeled through this parameters in a CAD environment. In the system, a hybrid programming approach is used. Generating and processing the point cloud, extraction of the gear parameters are performed by Visual BASIC programming language. 3D modeling in the CAD environment is performed also by AutoLISP programming language due to programming simplicity. These two softwares are provided to be in harmony by integrating them. In the study, SolidworksTM and AutoCADTM are selected as CAD environments. With this study, an alternative approach for the design of the spur gear is presented and modeling of the gears in the CAD environment is carried out using reverse engineering techniques.

The investment strategies of sovereign wealth funds: A reverse engineered pitch

Directory of Open Access Journals (Sweden)

Stanislav Martínek

2017-12-01

Full Text Available This letter describes personal reflection based on the utilization of the Faff’s (2017, Pitching Research pitch template for a reverse engineering technique in order to summarize, evaluate and properly interpret information from articles in respected scientific journals which represents key or seminal scientific research work upon which a researcher built his/her scientific work.

XIV Mediterranean Conference on Medical and Biological Engineering and Computing

CERN Document Server

Christofides, Stelios; Pattichis, Constantinos

2016-01-01

This volume presents the proceedings of Medicon 2016, held in Paphos, Cyprus. Medicon 2016 is the XIV in the series of regional meetings of the International Federation of Medical and Biological Engineering (IFMBE) in the Mediterranean. The goal of Medicon 2016 is to provide updated information on the state of the art on Medical and Biological Engineering and Computing under the main theme “Systems Medicine for the Delivery of Better Healthcare Services”. Medical and Biological Engineering and Computing cover complementary disciplines that hold great promise for the advancement of research and development in complex medical and biological systems. Research and development in these areas are impacting the science and technology by advancing fundamental concepts in translational medicine, by helping us understand human physiology and function at multiple levels, by improving tools and techniques for the detection, prevention and treatment of disease. Medicon 2016 provides a common platform for the cross fer...

Reverse engineering of B-pillar with 3D optical scanning for manufacturing of non-uniform thickness part

OpenAIRE

Islam Md. Tasbirul; Abdullah A.B.; Mahmud Mohamad Zihad

2017-01-01

This paper presents reverse engineering (RE) of a complex automobile structural part, B-pillar. As a major part of the automobile body-in white (BiW), B-pillar has substantial opportunity for weight reduction by introducing variable thickness across its sections. To leverage such potential, an existing B-pillar was reverse engineered with a 3D optical scanner and computer aided design (CAD) application. First, digital data (i.e. in meshes) of exiting B-pillar was obtained by the scanner, and ...

Plasma engineering design of a compact reversed-field pinch reactor (CRFPR)

International Nuclear Information System (INIS)

Bathke, C.G.; Embrechts, M.J.; Hagenson, R.L.; Krakowski, R.A.; Miller, R.L.

1983-01-01

The rationale for and the characteristics of the high-power-density Compact Reversed-Field Pinch Reactor (CRFPR) are discussed. Particular emphasis is given to key plasma engineering aspects of the conceptual design, including plasma operations, current drive, and impurity/ash control by means of pumped limiters or magnetic divertors. A brief description of the Fusion-Power-Core integration is given

Altering Height Data by Using Natural Logarithm as 3D Modelling Function for Reverse Engineering Application

Science.gov (United States)

Ilham Aminullah Abdulqawi, Nur; Salman Abu Mansor, Mohd

2018-01-01

The raw data extracted from reverse engineering based on vision mostly do not resemble the actual geometrical representation yet. Even though the higher object surface reflected the most visible light towards the camera and yield higher number of value based on Lambertian illumination model, this does not mean the curvature profile are always accurate. After all, there are many mathematical models to shape curvature profiles into the correct representation. However, one of the most appropriate models found is the natural logarithm function. The function itself has alteration properties towards the raw data generated from reverse engineering based on vision.

From biology to mathematical models and back: teaching modeling to biology students, and biology to math and engineering students.

Science.gov (United States)

Chiel, Hillel J; McManus, Jeffrey M; Shaw, Kendrick M

2010-01-01

We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a "live" textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology.

From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

Science.gov (United States)

McManus, Jeffrey M.; Shaw, Kendrick M.

2010-01-01

We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a “live” textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology. PMID:20810957

Analysis and simulation on two types of thrust reversers in an aircraft engine

Directory of Open Access Journals (Sweden)

Tian Feng

2017-01-01

Full Text Available With rapid development of new composite material and manufacturing, innovative engineering solutions are supplied to the advanced nacelle, such as integrated propulsion system(IPS, carbon-fiber composite inner skin by single-piece molding process，which offers a reduction in fuel burn and less noise produced by engines. The advanced nacelle has an O-duct thrust reverser demonstrator whose composite structure is in the form of an “O” as opposed to the traditional “D-duct”. A comparative study is to be conducted to investigate the differences between the latest O-duct and conventional D-duct in numerical approaches. To focus on the quantitative analysis of thrust reverser’s operation, this paper mainly uses CATIA/Digital Mock Up(DMU to simulate under deployment and stowed conditions of two different thrust reverser. After comparing the structural weight, the design models of blocker door are built for kinematic analysis of relevant mechanism and simulation. The results show that simplified design and elimination of multiple interfaces generates weight saving, O-duct improves airflows within the engine, meanwhile D-duct has excellent cost effective and maintainability.

Designing a 'neotissue' using the principles of biology, chemistry and engineering.

Science.gov (United States)

Nannaparaju, Madhusudhan; Oragui, Emeka; Khan, Wasim S

2012-01-01

The traditional methods of treating musculoskeletal injuries and disorders are not completely effective and have several limitations. Tissue engineering involves using the principles of biology, chemistry and engineering to design a 'neotissue' that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. In this review we provide an overview of the biology of common musculoskeletal tissue and discuss their common pathologies. We also describe the commonly used stem cells, scaffolds and bioreactors and evaluate their role in issue engineering.

Recent applications of synthetic biology tools for yeast metabolic engineering

DEFF Research Database (Denmark)

Jensen, Michael Krogh; Keasling, Jay

2015-01-01

to engineer microbial chemical factories has steadily decreased, improvement is still needed. Through the development of synthetic biology tools for key microbial hosts, it should be possible to further decrease the development times and improve the reliability of the resulting microorganism. Together...... with continuous decreases in price and improvements in DNA synthesis, assembly and sequencing, synthetic biology tools will rationalize time-consuming strain engineering, improve control of metabolic fluxes, and diversify screening assays for cellular metabolism. This review outlines some recently developed...... synthetic biology tools and their application to improve production of chemicals and fuels in yeast. Finally, we provide a perspective for the challenges that lie ahead....

Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

NARCIS (Netherlands)

He, F.; Murabito, E.; Westerhoff, H.V.

2016-01-01

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental

Proceedings of the European medical and biological engineering conference EMBEC '99 (Part I)

International Nuclear Information System (INIS)

Rehak, P.; Hutten, H.

1999-01-01

The proceedings books of the EMBEC '99 - European Medical and Biological Engineering Conference - are published in two parts as supplement 2 to the volume 37 of 'Medical and Biological Engineering and Computing', the official journal of the International Federation for Medical and Biological Engineering. More then 800 papers have been arranged in the order of the main topics and the topics of the special sessions of the conference. The paper of INIS relevance were worked up for INIS data bank. (author)

Geomagnetic polarity reversals as a mechanism for the punctuated equilibrium model of biological evolution

International Nuclear Information System (INIS)

Welsh, J.S.; Welsh, A.L.; Welsh, W.F.

2003-01-01

In contrast to what is predicted by classical Darwinian theory (phyletic gradualism), the fossil record typically displays a pattern of relatively sudden, dramatic changes as detailed by Eldregde and Gould's model of punctuated equilibrium. Evolutionary biologists have been at a loss to explain the ultimate source of the new mutations that drive evolution. One hypothesis holds that the abrupt speciation seen in the punctuated equilibrium model is secondary to an increased mutation rate resulting from periodically increased levels of ionizing radiation on the Earth's surface. Sporadic geomagnetic pole reversals, occurring every few million years on the average, are accompanied by alterations in the strength of the Earth's magnetic field and magnetosphere. This diminution may allow charged cosmic radiation to bombard Earth with less attenuation, thereby resulting in increased mutation rates. This episodic fluctuation in the magnetosphere is an attractive mechanism for the observed fossil record. Selected periods and epochs of geologic history for which data was available were reviewed for both geomagnetic pole reversal history and fossil record. Anomalies in either were scrutinized in greater depth and correlations were made. A 35 million year span (118-83 Ma) was identified during the Early/Middle Cretaceous period that was devoid of geomagnetic polarity reversals(the Cretaceous normal superchron). Examination of the fossil record (including several invertebrate and vertebrate taxons) during the Cretaceous normal superchron does not reveal any significant gap or slowing of speciation. Although increased terrestrial radiation exposure due to a diminution of the Earth's magnetosphere caused by a reversal of geomagnetic polarity is an attractive explanation for the mechanism of punctuated equilibrium, our investigation suggests that such polarity reversals cannot fully provide the driving force behind biological evolution. Further research is required to determine if

Cell-free synthetic biology for in vitro prototype engineering.

Science.gov (United States)

Moore, Simon J; MacDonald, James T; Freemont, Paul S

2017-06-15

Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

6th European Conference of the International Federation for Medical and Biological Engineering

CERN Document Server

Vasic, Darko

2015-01-01

This volume presents the Proceedings of the 6th European Conference of the International Federation for Medical and Biological Engineering (MBEC2014), held in Dubrovnik September 7 – 11, 2014. The general theme of MBEC 2014 is "Towards new horizons in biomedical engineering" The scientific discussions in these conference proceedings include the following themes: - Biomedical Signal Processing - Biomedical Imaging and Image Processing - Biosensors and Bioinstrumentation - Bio-Micro/Nano Technologies - Biomaterials - Biomechanics, Robotics and Minimally Invasive Surgery - Cardiovascular, Respiratory and Endocrine Systems Engineering - Neural and Rehabilitation Engineering - Molecular, Cellular and Tissue Engineering - Bioinformatics and Computational Biology - Clinical Engineering and Health Technology Assessment - Health Informatics, E-Health and Telemedicine - Biomedical Engineering Education

Reverse-engineering of gene networks for regulating early blood development from single-cell measurements.

Science.gov (United States)

Wei, Jiangyong; Hu, Xiaohua; Zou, Xiufen; Tian, Tianhai

2017-12-28

Recent advances in omics technologies have raised great opportunities to study large-scale regulatory networks inside the cell. In addition, single-cell experiments have measured the gene and protein activities in a large number of cells under the same experimental conditions. However, a significant challenge in computational biology and bioinformatics is how to derive quantitative information from the single-cell observations and how to develop sophisticated mathematical models to describe the dynamic properties of regulatory networks using the derived quantitative information. This work designs an integrated approach to reverse-engineer gene networks for regulating early blood development based on singel-cell experimental observations. The wanderlust algorithm is initially used to develop the pseudo-trajectory for the activities of a number of genes. Since the gene expression data in the developed pseudo-trajectory show large fluctuations, we then use Gaussian process regression methods to smooth the gene express data in order to obtain pseudo-trajectories with much less fluctuations. The proposed integrated framework consists of both bioinformatics algorithms to reconstruct the regulatory network and mathematical models using differential equations to describe the dynamics of gene expression. The developed approach is applied to study the network regulating early blood cell development. A graphic model is constructed for a regulatory network with forty genes and a dynamic model using differential equations is developed for a network of nine genes. Numerical results suggests that the proposed model is able to match experimental data very well. We also examine the networks with more regulatory relations and numerical results show that more regulations may exist. We test the possibility of auto-regulation but numerical simulations do not support the positive auto-regulation. In addition, robustness is used as an importantly additional criterion to select candidate

From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

Science.gov (United States)

Chiel, Hillel J.; McManus, Jeffrey M.; Shaw, Kendrick M.

2010-01-01

We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge…

A novel technique for presurgical nasoalveolar molding using computer-aided reverse engineering and rapid prototyping.

Science.gov (United States)

Yu, Quan; Gong, Xin; Wang, Guo-Min; Yu, Zhe-Yuan; Qian, Yu-Fen; Shen, Gang

2011-01-01

To establish a new method of presurgical nasoalveolar molding (NAM) using computer-aided reverse engineering and rapid prototyping technique in infants with unilateral cleft lip and palate (UCLP). Five infants (2 males and 3 females with mean age of 1.2 w) with complete UCLP were recruited. All patients were subjected to NAM before the cleft lip repair. The upper denture casts were recorded using a three-dimensional laser scanner within 2 weeks after birth in UCLP infants. A digital model was constructed and analyzed to simulate the NAM procedure with reverse engineering software. The digital geometrical data were exported to print the solid model with rapid prototyping system. The whole set of appliances was fabricated based on these solid models. Laser scanning and digital model construction simplified the NAM procedure and estimated the treatment objective. The appliances were fabricated based on the rapid prototyping technique, and for each patient, the complete set of appliances could be obtained at one time. By the end of presurgical NAM treatment, the cleft was narrowed, and the malformation of nasoalveolar segments was aligned normally. We have developed a novel technique of presurgical NAM based on a computer-aided design. The accurate digital denture model of UCLP infants could be obtained with laser scanning. The treatment design and appliance fabrication could be simplified with a computer-aided reverse engineering and rapid prototyping technique.

Reverse engineering of inductive fault current limiters

Energy Technology Data Exchange (ETDEWEB)

Pina, J M; Neves, M Ventim; Rodrigues, A L [Centre of Technology and Systems Faculdade de Ciencias e Tecnologia, Nova University of Lisbon Monte de Caparica, 2829-516 Caparica (Portugal); Suarez, P; Alvarez, A, E-mail: jmmp@fct.unl.p [' Benito Mahedero' Group of Electrical Applications of Superconductors Escuela de IngenierIas Industrials, University of Extremadura Avenida de Elvas s/n, 06006 Badajoz (Spain)

2010-06-01

The inductive fault current limiter is less compact and harder to scale to high voltage networks than the resistive one. Nevertheless, its simple construction and mechanical robustness make it attractive in low voltage grids. Thus, it might be an enabling technology for the advent of microgrids, low voltage networks with dispersed generation, controllable loads and energy storage. A new methodology for reverse engineering of inductive fault current limiters based on the independent analysis of iron cores and HTS cylinders is presented in this paper. Their electromagnetic characteristics are used to predict the devices' hysteresis loops and consequently their dynamic behavior. Previous models based on the separate analysis of the limiters' components were already derived, e.g. in transformer like equivalent models. Nevertheless, the assumptions usually made may limit these models' application, as shown in the paper. The proposed methodology obviates these limitations. Results are validated through simulations.

Reverse engineering of inductive fault current limiters

International Nuclear Information System (INIS)

Pina, J M; Neves, M Ventim; Rodrigues, A L; Suarez, P; Alvarez, A

2010-01-01

The inductive fault current limiter is less compact and harder to scale to high voltage networks than the resistive one. Nevertheless, its simple construction and mechanical robustness make it attractive in low voltage grids. Thus, it might be an enabling technology for the advent of microgrids, low voltage networks with dispersed generation, controllable loads and energy storage. A new methodology for reverse engineering of inductive fault current limiters based on the independent analysis of iron cores and HTS cylinders is presented in this paper. Their electromagnetic characteristics are used to predict the devices' hysteresis loops and consequently their dynamic behavior. Previous models based on the separate analysis of the limiters' components were already derived, e.g. in transformer like equivalent models. Nevertheless, the assumptions usually made may limit these models' application, as shown in the paper. The proposed methodology obviates these limitations. Results are validated through simulations.

Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

DEFF Research Database (Denmark)

Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

2016-01-01

Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

Directory of Open Access Journals (Sweden)

Lihong Jiang

2018-06-01

Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

Graphical User Interfaces Reverse Engineering for Requirements Elicitation - Literature Review

Directory of Open Access Journals (Sweden)

Carol Jaimes

2016-06-01

Full Text Available This paper exhibits a synthesis of the use of legacy systems GUI reverse engineering as a tool to software requirements elicitation. It presents a literature review describing the approaches related to the topic. This work primary goal is to determine the major investigations in this area, and if there are techniques focused exclusively on the observation of the legacy applications GUI to obtain software requirements in a standard format, without the use of source code, data structures, documentation or sophisticated algorithms for the application analysis.

Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions.

Science.gov (United States)

Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Liu, Long

By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

Reversing flow catalytic converter for a natural gas/diesel dual fuel engine

Energy Technology Data Exchange (ETDEWEB)

Liu, E.; Checkel, M.D. [Alberta Univ., Edmonton, AB (Canada). Dept. of Mechanical Engineering; Hayes, R.E. [Alberta Univ., Edmonton, AB (Canada). Dept. of Chemical and Materials Engineering; Alberta Univ., Edmonton, AB (Canada). Dept. of Mechanical Engineering; Zheng, M.; Mirosh, E. [Alternative Fuel Systems Inc., Calgary, AB (Canada)

2001-07-01

An experimental and modelling study was performed for a reverse flow catalytic converter attached to a natural gas/diesel dual fuel engine. The catalytic converter had a segmented ceramic monolith honeycomb substrate and a catalytic washcoat containing a predominantly palladium catalyst. A one-dimensional single channel model was used to simulate the operation of the converter. The kinetics of the CO and methane oxidation followed first-order behaviour. The activation energy for the oxidation of methane showed a change with temperature, dropping from a value of 129 to 35 kJ/mol at a temperature of 874 K. The reverse flow converter was able to achieve high reactor temperature under conditions of low inlet gas temperature, provided that the initial reactor temperature was sufficiently high. (author)

Biotechnology and synthetic biology approaches for metabolic engineering of bioenergy crops.

Science.gov (United States)

Shih, Patrick M; Liang, Yan; Loqué, Dominique

2016-07-01

The Green Revolution has fuelled an exponential growth in human population since the mid-20th century. Due to population growth, food and energy demands will soon surpass supply capabilities. To overcome these impending problems, significant improvements in genetic engineering will be needed to complement breeding efforts in order to accelerate the improvement of agronomical traits. The new field of plant synthetic biology has emerged in recent years and is expected to support rapid, precise, and robust engineering of plants. In this review, we present recent advances made in the field of plant synthetic biology, specifically in genome editing, transgene expression regulation, and bioenergy crop engineering, with a focus on traits related to lignocellulose, oil, and soluble sugars. Ultimately, progress and innovation in these fields may facilitate the development of beneficial traits in crop plants to meet society's bioenergy needs. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study

Directory of Open Access Journals (Sweden)

Gaurav Sharma

2008-11-01

Full Text Available Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis11Department of Mechanical and Industrial Engineering; 4Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA; 2The Center for Engineering in Medicine (CEM, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 3Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA; 5Department of Biomedical Engineering, Rutgers University, NJ, USAAbstract: We describe the molecular dynamics (MD-aided engineering design of mutant peptides based on the α-helical coiled-coil GCN4 leucine zipper peptide (GCN4-p1 in order to obtain environmentally-responsive nanotweezers. The actuation mechanism of the nanotweezers depends on the modification of electrostatic charges on the residues along the length of the coiled coil. Modulating the solution pH between neutral and acidic values results in the reversible movement of helices toward and away from each other and creates a complete closed-open-closed transition cycle between the helices. Our results indicate that the mutants show a reversible opening of up to 15 Å (1.5 nm; approximately 150% of the initial separation upon pH actuation. Investigation on the physicochemical phenomena that influence conformational properties, structural stability, and reversibility of the coiled-coil peptide-based nanotweezers revealed that a rationale- and design-based approach is needed to engineer stable peptide or macromolecules into stimuli-responsive devices. The efficacy of the mutant that demonstrated the most significant reversible actuation for environmentally responsive modulation of DNA-binding activity was also demonstrated. Our results have significant implications in bioseparations and in the engineering of novel transcription factors.Keywords: bionanotechnology, nanotweezers, coiled-coil, GCN4, leucine zipper, molecular dynamics, environmentally

[Veneer computer aided design based on reverse engineering technology].

Science.gov (United States)

Liu, Ming-li; Chen, Xiao-dong; Wang, Yong

2012-03-01

To explore the computer aided design (CAD) method of veneer restoration, and to assess if the solution can help prosthesis meet morphology esthetics standard. A volunteer's upper right central incisor needed to be restored with veneer. Super hard stone models of patient's dentition (before and after tooth preparation) were scanned with the three-dimensional laser scanner. The veneer margin was designed as butt-to-butt type. The veneer was constructed using reverse engineering (RE) software. The technique guideline of veneers CAD was explore based on RE software, and the veneers was smooth, continuous and symmetrical, which met esthetics construction needs. It was a feasible method to reconstruct veneer restoration based on RE technology.

An approach for reduction of false predictions in reverse engineering of gene regulatory networks.

Science.gov (United States)

Khan, Abhinandan; Saha, Goutam; Pal, Rajat Kumar

2018-05-14

A gene regulatory network discloses the regulatory interactions amongst genes, at a particular condition of the human body. The accurate reconstruction of such networks from time-series genetic expression data using computational tools offers a stiff challenge for contemporary computer scientists. This is crucial to facilitate the understanding of the proper functioning of a living organism. Unfortunately, the computational methods produce many false predictions along with the correct predictions, which is unwanted. Investigations in the domain focus on the identification of as many correct regulations as possible in the reverse engineering of gene regulatory networks to make it more reliable and biologically relevant. One way to achieve this is to reduce the number of incorrect predictions in the reconstructed networks. In the present investigation, we have proposed a novel scheme to decrease the number of false predictions by suitably combining several metaheuristic techniques. We have implemented the same using a dataset ensemble approach (i.e. combining multiple datasets) also. We have employed the proposed methodology on real-world experimental datasets of the SOS DNA Repair network of Escherichia coli and the IMRA network of Saccharomyces cerevisiae. Subsequently, we have experimented upon somewhat larger, in silico networks, namely, DREAM3 and DREAM4 Challenge networks, and 15-gene and 20-gene networks extracted from the GeneNetWeaver database. To study the effect of multiple datasets on the quality of the inferred networks, we have used four datasets in each experiment. The obtained results are encouraging enough as the proposed methodology can reduce the number of false predictions significantly, without using any supplementary prior biological information for larger gene regulatory networks. It is also observed that if a small amount of prior biological information is incorporated here, the results improve further w.r.t. the prediction of true positives

Genome Engineering and Modification Toward Synthetic Biology for the Production of Antibiotics.

Science.gov (United States)

Zou, Xuan; Wang, Lianrong; Li, Zhiqiang; Luo, Jie; Wang, Yunfu; Deng, Zixin; Du, Shiming; Chen, Shi

2018-01-01

Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics. © 2017 Wiley Periodicals, Inc.

An Evaluation of Active Learning Causal Discovery Methods for Reverse-Engineering Local Causal Pathways of Gene Regulation

Science.gov (United States)

Ma, Sisi; Kemmeren, Patrick; Aliferis, Constantin F.; Statnikov, Alexander

2016-01-01

Reverse-engineering of causal pathways that implicate diseases and vital cellular functions is a fundamental problem in biomedicine. Discovery of the local causal pathway of a target variable (that consists of its direct causes and direct effects) is essential for effective intervention and can facilitate accurate diagnosis and prognosis. Recent research has provided several active learning methods that can leverage passively observed high-throughput data to draft causal pathways and then refine the inferred relations with a limited number of experiments. The current study provides a comprehensive evaluation of the performance of active learning methods for local causal pathway discovery in real biological data. Specifically, 54 active learning methods/variants from 3 families of algorithms were applied for local causal pathways reconstruction of gene regulation for 5 transcription factors in S. cerevisiae. Four aspects of the methods’ performance were assessed, including adjacency discovery quality, edge orientation accuracy, complete pathway discovery quality, and experimental cost. The results of this study show that some methods provide significant performance benefits over others and therefore should be routinely used for local causal pathway discovery tasks. This study also demonstrates the feasibility of local causal pathway reconstruction in real biological systems with significant quality and low experimental cost. PMID:26939894

Multiplexed genome engineering and genotyping methods applications for synthetic biology and metabolic engineering.

Science.gov (United States)

Wang, Harris H; Church, George M

2011-01-01

Engineering at the scale of whole genomes requires fundamentally new molecular biology tools. Recent advances in recombineering using synthetic oligonucleotides enable the rapid generation of mutants at high efficiency and specificity and can be implemented at the genome scale. With these techniques, libraries of mutants can be generated, from which individuals with functionally useful phenotypes can be isolated. Furthermore, populations of cells can be evolved in situ by directed evolution using complex pools of oligonucleotides. Here, we discuss ways to utilize these multiplexed genome engineering methods, with special emphasis on experimental design and implementation. Copyright © 2011 Elsevier Inc. All rights reserved.

Plant synthetic biology for molecular engineering of signalling and development.

Science.gov (United States)

Nemhauser, Jennifer L; Torii, Keiko U

2016-03-02

Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions.

Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

Science.gov (United States)

Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

2012-02-26

The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

SYSTEMS BIOLOGY AND METABOLIC ENGINEERING OF ARTHROSPIRA CELL FACTORIES

Directory of Open Access Journals (Sweden)

Amornpan Klanchui

2012-10-01

Full Text Available Arthrospira are attractive candidates to serve as cell factories for production of many valuable compounds useful for food, feed, fuel and pharmaceutical industries. In connection with the development of sustainable bioprocessing, it is a challenge to design and develop efficient Arthrospira cell factories which can certify effective conversion from the raw materials (i.e. CO2 and sun light into desired products. With the current availability of the genome sequences and metabolic models of Arthrospira, the development of Arthrospira factories can now be accelerated by means of systems biology and the metabolic engineering approach. Here, we review recent research involving the use of Arthrospira cell factories for industrial applications, as well as the exploitation of systems biology and the metabolic engineering approach for studying Arthrospira. The current status of genomics and proteomics through the development of the genome-scale metabolic model of Arthrospira, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies are discussed. At the end, the perspective and future direction on Arthrospira cell factories for industrial biotechnology are presented.

An Analytical Reverse Engineering of IELTS Listening Tasks for a Construct Model

OpenAIRE

Masood Khalili Sabet; Hamid Reza Babaee Bormanaki

2017-01-01

The study reported here was concerned with the issue of reverse engineering of language test items as it relates to the identification of the language constructs underlying listening tasks of LELTS test. In this regard, the IELTS examination papers, from IELTS 1 to IELTS 10 were compiled as a corpus for the analysis. Tasks were analyzed using a taxonomic frame work adopted from Moore, Morton and price (2012), that was originally adapted from Weir and Urquhart (1998), with a focus on two dimen...

A reverse engineering approach to optimize experiments for the construction of biological regulatory networks.

Science.gov (United States)

Zhang, Xiaomeng; Shao, Bin; Wu, Yangle; Qi, Ouyang

2013-01-01

One of the major objectives in systems biology is to understand the relation between the topological structures and the dynamics of biological regulatory networks. In this context, various mathematical tools have been developed to deduct structures of regulatory networks from microarray expression data. In general, from a single data set, one cannot deduct the whole network structure; additional expression data are usually needed. Thus how to design a microarray expression experiment in order to get the most information is a practical problem in systems biology. Here we propose three methods, namely, maximum distance method, trajectory entropy method, and sampling method, to derive the optimal initial conditions for experiments. The performance of these methods is tested and evaluated in three well-known regulatory networks (budding yeast cell cycle, fission yeast cell cycle, and E. coli. SOS network). Based on the evaluation, we propose an efficient strategy for the design of microarray expression experiments.

CellNet: Network Biology Applied to Stem Cell Engineering

Science.gov (United States)

Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

2014-01-01

SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793

CellNet: network biology applied to stem cell engineering.

Science.gov (United States)

Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

2014-08-14

Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

Topology reconstruction for B-Rep modeling from 3D mesh in reverse engineering applications

Science.gov (United States)

Bénière, Roseline; Subsol, Gérard; Gesquière, Gilles; Le Breton, François; Puech, William

2012-03-01

Nowadays, most of the manufactured objects are designed using CAD (Computer-Aided Design) software. Nevertheless, for visualization, data exchange or manufacturing applications, the geometric model has to be discretized into a 3D mesh composed of a finite number of vertices and edges. But, in some cases, the initial model may be lost or unavailable. In other cases, the 3D discrete representation may be modified, for example after a numerical simulation, and does not correspond anymore to the initial model. A reverse engineering method is then required to reconstruct a 3D continuous representation from the discrete one. In previous work, we have presented a new approach for 3D geometric primitive extraction. In this paper, to complete our automatic and comprehensive reverse engineering process, we propose a method to construct the topology of the retrieved object. To reconstruct a B-Rep model, a new formalism is now introduced to define the adjacency relations. Then a new process is used to construct the boundaries of the object. The whole process is tested on 3D industrial meshes and bring a solution to recover B-Rep models.

Review of Microfluidic Photobioreactor Technology for Metabolic Engineering and Synthetic Biology of Cyanobacteria and Microalgae

Directory of Open Access Journals (Sweden)

Ya-Tang Yang

2016-10-01

Full Text Available One goal of metabolic engineering and synthetic biology for cyanobacteria and microalgae is to engineer strains that can optimally produce biofuels and commodity chemicals. However, the current workflow is slow and labor intensive with respect to assembly of genetic parts and characterization of production yields because of the slow growth rates of these organisms. Here, we review recent progress in the microfluidic photobioreactors and identify opportunities and unmet needs in metabolic engineering and synthetic biology. Because of the unprecedented experimental resolution down to the single cell level, long-term real-time monitoring capability, and high throughput with low cost, microfluidic photobioreactor technology will be an indispensible tool to speed up the development process, advance fundamental knowledge, and realize the full potential of metabolic engineering and synthetic biology for cyanobacteria and microalgae.

A reverse engineering methodology for nickel alloy turbine blades with internal features

DEFF Research Database (Denmark)

Gameros, A.; De Chiffre, Leonardo; Siller, H.R.

2015-01-01

The scope of this work is to present a reverse engineering (RE) methodology for freeform surfaces, based on a case study of a turbine blade made of Inconel, including the reconstruction of its internal cooling system. The methodology uses an optical scanner and X-ray computed tomography (CT......) equipment. Traceability of the measurements was obtained through the use of a Modular Freeform Gage (MFG). An uncertainty budget is presented for both measuring technologies and results show that the RE methodology presented is promising when comparing uncertainty values against common industrial tolerances....

The Future of Metabolic Engineering and Synthetic Biology: Towards a Systematic Practice

Science.gov (United States)

Yadav, Vikramaditya G.; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

2012-01-01

Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. PMID:22629571

Using a Formal Approach for Reverse Engineering and Design Recovery to Support Software Reuse

Science.gov (United States)

Gannod, Gerald C.

2002-01-01

This document describes 3rd year accomplishments and summarizes overall project accomplishments. Included as attachments are all published papers from year three. Note that the budget for this project was discontinued after year two, but that a residual budget from year two allowed minimal continuance into year three. Accomplishments include initial investigations into log-file based reverse engineering, service-based software reuse, and a source to XML generator.

The future of metabolic engineering and synthetic biology: towards a systematic practice.

Science.gov (United States)

Yadav, Vikramaditya G; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

2012-05-01

Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as 'multivariate modular metabolic engineering' (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. Copyright © 2011 Elsevier Inc. All rights reserved.

An analysis of extended entity relationship constructs extraction in database reverse engineering approaches

International Nuclear Information System (INIS)

Jilani, M.A.; Aziz, A.; Hussain, T.

2008-01-01

Database reverse Engineering is technique used for transforming relational schema into a conceptual schema for finding and fixing design flaw for maintaining and re-engineering database systems for the integration of database system with another and migration of a database system from one platform to another. We studied the approaches from year 1993 to 2006 to find out which EER construct cannot be retrieved by most of the DBRE approaches so that they can be retrieved in the future. For each EER construct that can be retrieved by using a given DBRE approach. We show whether they are retrieved without user involvement (automatically). Partial user involvement (semi-automatically) or full user involvement (manually). We also discuss the relevant advantages and limitations of each DBRE technique considered in this paper. (author)

Engineering biological systems toward a sustainable bioeconomy.

Science.gov (United States)

Lopes, Mateus Schreiner Garcez

2015-06-01

The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

Internet-based dimensional verification system for reverse engineering processes

International Nuclear Information System (INIS)

Song, In Ho; Kim, Kyung Don; Chung, Sung Chong

2008-01-01

This paper proposes a design methodology for a Web-based collaborative system applicable to reverse engineering processes in a distributed environment. By using the developed system, design reviewers of new products are able to confirm geometric shapes, inspect dimensional information of products through measured point data, and exchange views with other design reviewers on the Web. In addition, it is applicable to verifying accuracy of production processes by manufacturing engineers. Functional requirements for designing this Web-based dimensional verification system are described in this paper. ActiveX-server architecture and OpenGL plug-in methods using ActiveX controls realize the proposed system. In the developed system, visualization and dimensional inspection of the measured point data are done directly on the Web: conversion of the point data into a CAD file or a VRML form is unnecessary. Dimensional verification results and design modification ideas are uploaded to markups and/or XML files during collaboration processes. Collaborators review the markup results created by others to produce a good design result on the Web. The use of XML files allows information sharing on the Web to be independent of the platform of the developed system. It is possible to diversify the information sharing capability among design collaborators. Validity and effectiveness of the developed system has been confirmed by case studies

Internet-based dimensional verification system for reverse engineering processes

Energy Technology Data Exchange (ETDEWEB)

Song, In Ho [Ajou University, Suwon (Korea, Republic of); Kim, Kyung Don [Small Business Corporation, Suwon (Korea, Republic of); Chung, Sung Chong [Hanyang University, Seoul (Korea, Republic of)

2008-07-15

This paper proposes a design methodology for a Web-based collaborative system applicable to reverse engineering processes in a distributed environment. By using the developed system, design reviewers of new products are able to confirm geometric shapes, inspect dimensional information of products through measured point data, and exchange views with other design reviewers on the Web. In addition, it is applicable to verifying accuracy of production processes by manufacturing engineers. Functional requirements for designing this Web-based dimensional verification system are described in this paper. ActiveX-server architecture and OpenGL plug-in methods using ActiveX controls realize the proposed system. In the developed system, visualization and dimensional inspection of the measured point data are done directly on the Web: conversion of the point data into a CAD file or a VRML form is unnecessary. Dimensional verification results and design modification ideas are uploaded to markups and/or XML files during collaboration processes. Collaborators review the markup results created by others to produce a good design result on the Web. The use of XML files allows information sharing on the Web to be independent of the platform of the developed system. It is possible to diversify the information sharing capability among design collaborators. Validity and effectiveness of the developed system has been confirmed by case studies

Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

Directory of Open Access Journals (Sweden)

Laura R. Jarboe

2010-01-01

Full Text Available Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors.

Engineering Liposomes and Nanoparticles for Biological Targeting

DEFF Research Database (Denmark)

Jølck, Rasmus Irming; Feldborg, Lise Nørkjær; Andersen, Simon

2011-01-01

Our ability to engineer nanomaterials for biological and medical applications is continuously increasing, and nanomaterial designs are becoming more and more complex. One very good example of this is the drug delivery field where nanoparticle systems can be used to deliver drugs specifically...... to diseased tissue. In the early days, the design of the nanoparticles was relatively simple, but today we can surface functionalize and manipulate material properties to target diseased tissue and build highly complex drug release mechanisms into our designs. One of the most promising strategies in drug...

Reverse Engineering Nature to Design Biomimetic Total Knee Implants.

Science.gov (United States)

Varadarajan, Kartik Mangudi; Zumbrunn, Thomas; Rubash, Harry E; Malchau, Henrik; Muratoglu, Orhun K; Li, Guoan

2015-10-01

While contemporary total knee arthroplasty (TKA) provides tremendous clinical benefits, the normal feel and function of the knee is not fully restored. To address this, a novel design process was developed to reverse engineer "biomimetic" articular surfaces that are compatible with normal soft-tissue envelope and kinematics of the knee. The biomimetic articular surface is created by moving the TKA femoral component along in vivo kinematics of normal knees and carving out the tibial articular surface from a rectangular tibial block. Here, we describe the biomimetic design process. In addition, we utilize geometric comparisons and kinematic simulations to show that; (1) tibial articular surfaces of conventional implants are fundamentally incompatible with normal knee motion, and (2) the anatomic geometry of the biomimetic surface contributes directly to restoration of normal knee kinematics. Such biomimetic implants may enable us to achieve the long sought after goal of a "normal" knee post-TKA surgery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Smartphone based scalable reverse engineering by digital image correlation

Science.gov (United States)

Vidvans, Amey; Basu, Saurabh

2018-03-01

There is a need for scalable open source 3D reconstruction systems for reverse engineering. This is because most commercially available reconstruction systems are capital and resource intensive. To address this, a novel reconstruction technique is proposed. The technique involves digital image correlation based characterization of surface speeds followed by normalization with respect to angular speed during rigid body rotational motion of the specimen. Proof of concept of the same is demonstrated and validated using simulation and empirical characterization. Towards this, smart-phone imaging and inexpensive off the shelf components along with those fabricated additively using poly-lactic acid polymer with a standard 3D printer are used. Some sources of error in this reconstruction methodology are discussed. It is seen that high curvatures on the surface suppress accuracy of reconstruction. Reasons behind this are delineated in the nature of the correlation function. Theoretically achievable resolution during smart-phone based 3D reconstruction by digital image correlation is derived.

BioCarian: search engine for exploratory searches in heterogeneous biological databases.

Science.gov (United States)

Zaki, Nazar; Tennakoon, Chandana

2017-10-02

There are a large number of biological databases publicly available for scientists in the web. Also, there are many private databases generated in the course of research projects. These databases are in a wide variety of formats. Web standards have evolved in the recent times and semantic web technologies are now available to interconnect diverse and heterogeneous sources of data. Therefore, integration and querying of biological databases can be facilitated by techniques used in semantic web. Heterogeneous databases can be converted into Resource Description Format (RDF) and queried using SPARQL language. Searching for exact queries in these databases is trivial. However, exploratory searches need customized solutions, especially when multiple databases are involved. This process is cumbersome and time consuming for those without a sufficient background in computer science. In this context, a search engine facilitating exploratory searches of databases would be of great help to the scientific community. We present BioCarian, an efficient and user-friendly search engine for performing exploratory searches on biological databases. The search engine is an interface for SPARQL queries over RDF databases. We note that many of the databases can be converted to tabular form. We first convert the tabular databases to RDF. The search engine provides a graphical interface based on facets to explore the converted databases. The facet interface is more advanced than conventional facets. It allows complex queries to be constructed, and have additional features like ranking of facet values based on several criteria, visually indicating the relevance of a facet value and presenting the most important facet values when a large number of choices are available. For the advanced users, SPARQL queries can be run directly on the databases. Using this feature, users will be able to incorporate federated searches of SPARQL endpoints. We used the search engine to do an exploratory search

Prevention of Preharvest Sprouting through Hormone Engineering and Germination Recovery by Chemical Biology.

Science.gov (United States)

Nonogaki, Mariko; Nonogaki, Hiroyuki

2017-01-01

Vivipary, germination of seeds on the maternal plant, is observed in nature and provides ecological advantages in certain wild species, such as mangroves. However, precocious seed germination in agricultural species, such as preharvest sprouting (PHS) in cereals, is a serious issue for food security. PHS reduces grain quality and causes economical losses to farmers. PHS can be prevented by translating the basic knowledge of hormone biology in seeds into technologies. Biosynthesis of abscisic acid (ABA), which is an essential hormone for seed dormancy, can be engineered to enhance dormancy and prevent PHS. Enhancing nine- cis -epoxycarotenoid dioxygenase (NCED), a rate-limiting enzyme of ABA biosynthesis, through a chemically induced gene expression system, has successfully been used to suppress germination of Arabidopsis seeds. The more advanced system NCED positive-feedback system, which amplifies ABA biosynthesis in a seed-specific manner without chemical induction, has also been developed. The proofs of concept established in the model species are now ready to be applied to crops. A potential problem is recovery of germination from hyperdormant crop grains. Hyperdormancy induced by the NCED systems can be reversed by inducing counteracting genes, such as NCED RNA interference or gibberellin (GA) biosynthesis genes. Alternatively, seed sensitivity to ABA can be modified to rescue germination using the knowledge of chemical biology. ABA antagonists, which were developed recently, have great potential to recover germination from the hyperdormant seeds. Combination of the dormancy-imposing and -releasing approaches will establish a comprehensive technology for PHS prevention and germination recovery.

Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

Energy Technology Data Exchange (ETDEWEB)

Silver, Pamela [Harvard Univ., Cambridge, MA (United States); SEED 2015 Conference Chair; Flach, Evan [American Institute of Chemical Engineers; SEED 2015 Conference Organizer

2016-10-27

Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international

Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology

DEFF Research Database (Denmark)

Dvořák, Pavel; Nikel, Pablo Ivan; Damborskýc, Jiří

2017-01-01

pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack...... of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow....... In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering...

Advancing the science of forest hydrology A challenge to agricultural and biological engineers

Science.gov (United States)

Devendra Amatya; Wayne Skaggs; Carl Trettin

2009-01-01

For more than a century, agricultural and biological engineers have provided major advances in science, engineering, and technology to increase food and fiber production to meet the demands of a rapidly growing global population. The land base for these technological advances has originated largely from forested lands, which have experienced dramatic declines over the...

Reverse engineering of B-pillar with 3D optical scanning for manufacturing of non-uniform thickness part

Directory of Open Access Journals (Sweden)

Islam Md. Tasbirul

2017-01-01

Full Text Available This paper presents reverse engineering (RE of a complex automobile structural part, B-pillar. As a major part of the automobile body-in white (BiW, B-pillar has substantial opportunity for weight reduction by introducing variable thickness across its sections. To leverage such potential, an existing B-pillar was reverse engineered with a 3D optical scanner and computer aided design (CAD application. First, digital data (i.e. in meshes of exiting B-pillar was obtained by the scanner, and subsequently, this information was utilized in developing a complete 3D CAD model. CATIA V5 was used in the modeling where some of the essential work benches were “Digitized Shape Editor”, “Quick Surface Reconstruction”, “Wireframe and Surface Design”, “Freestyle”, “Generation Shape Design” and “Part design”. In the final CAD design, five different thicknesses were incorporated successfully in order to get a B-pillar with non-uniform sections. This research opened opportunities for thickness optimization and mold tooling design in real time manufacturing.

Introducing Molecular Biology to Environmental Engineers through Development of a New Course.

Science.gov (United States)

Oerther, Daniel B.

2002-01-01

Introduces a molecular biology course designed for environmental engineering majors using 16S ribosomal ribonucleic acid-targeted technology that allows students to identify and study microorganisms in bioreactor environments. (Contains 17 references.) (YDS)

A swarm intelligence framework for reconstructing gene networks: searching for biologically plausible architectures.

Science.gov (United States)

Kentzoglanakis, Kyriakos; Poole, Matthew

2012-01-01

In this paper, we investigate the problem of reverse engineering the topology of gene regulatory networks from temporal gene expression data. We adopt a computational intelligence approach comprising swarm intelligence techniques, namely particle swarm optimization (PSO) and ant colony optimization (ACO). In addition, the recurrent neural network (RNN) formalism is employed for modeling the dynamical behavior of gene regulatory systems. More specifically, ACO is used for searching the discrete space of network architectures and PSO for searching the corresponding continuous space of RNN model parameters. We propose a novel solution construction process in the context of ACO for generating biologically plausible candidate architectures. The objective is to concentrate the search effort into areas of the structure space that contain architectures which are feasible in terms of their topological resemblance to real-world networks. The proposed framework is initially applied to the reconstruction of a small artificial network that has previously been studied in the context of gene network reverse engineering. Subsequently, we consider an artificial data set with added noise for reconstructing a subnetwork of the genetic interaction network of S. cerevisiae (yeast). Finally, the framework is applied to a real-world data set for reverse engineering the SOS response system of the bacterium Escherichia coli. Results demonstrate the relative advantage of utilizing problem-specific knowledge regarding biologically plausible structural properties of gene networks over conducting a problem-agnostic search in the vast space of network architectures.

Synthetic biology: a challenge to mechanical explanations in biology?

Science.gov (United States)

Morange, Michel

2012-01-01

In their plans to modify organisms, synthetic biologists have contrasted engineering and tinkering. By drawing this contrast between their endeavors and what has happened during the evolution of organisms by natural selection, they underline the novelty of their projects and justify their ambitions. Synthetic biologists are at odds with a long tradition that has considered organisms as "perfect machines." This tradition had already been questioned by Stephen Jay Gould in the 1970s and received a major blow with the comparison made by François Jacob between organisms and the results of "bricolage" (tinkering). These contrasts between engineering and tinkering, synthetic biology and evolution, have no raison d'être. Machines built by humans are increasingly inspired by observations made on organisms. This is not a simple reversal of the previous trend-the mechanical conception of organisms-in which the characteristics of the latter were explained by comparison with human-built machines. Relations between organisms and machines have always been complex and ambiguous.

The development of a program analysis environment for Ada: Reverse engineering tools for Ada

Science.gov (United States)

Cross, James H., II

1991-01-01

The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2014

Energy Technology Data Exchange (ETDEWEB)

Voigt, Christopher [Massachusetts Institute of Technology

2014-07-01

SEED2014 focused on advances in the science and technology emerging from the field of synthetic biology. We broadly define this as technologies that accelerate the process of genetic engineering. It highlighted new tool development, as well as the application of these tools to diverse problems in biotechnology, including therapeutics, industrial chemicals and fuels, natural products, and agriculture. Systems spanned from in vitro experiments and viruses, through diverse bacteria, to eukaryotes (yeast, mammalian cells, plants).

Automatic Reverse Engineering of Private Flight Control Protocols of UAVs

Directory of Open Access Journals (Sweden)

Ran Ji

2017-01-01

Full Text Available The increasing use of civil unmanned aerial vehicles (UAVs has the potential to threaten public safety and privacy. Therefore, airspace administrators urgently need an effective method to regulate UAVs. Understanding the meaning and format of UAV flight control commands by automatic protocol reverse-engineering techniques is highly beneficial to UAV regulation. To improve our understanding of the meaning and format of UAV flight control commands, this paper proposes a method to automatically analyze the private flight control protocols of UAVs. First, we classify flight control commands collected from a binary network trace into clusters; then, we analyze the meaning of flight control commands by the accumulated error of each cluster; next, we extract the binary format of commands and infer field semantics in these commands; and finally, we infer the location of the check field in command and the generator polynomial matrix. The proposed approach is validated via experiments on a widely used consumer UAV.

5th European Conference of the International Federation for Medical and Biological Engineering

CERN Document Server

European IFMBE MBEC : Cooperation for Effective Healthcare

2012-01-01

This volume presents the 5th European Conference of the International Federation for Medical and Biological Engineering (EMBEC),  held in Budapest, 14-18 September, 2011. The scientific discussion on the conference and in this conference proceedings include the following issues: - Signal & Image Processing - ICT - Clinical Engineering and Applications - Biomechanics and Fluid Biomechanics - Biomaterials and Tissue Repair - Innovations and Nanotechnology - Modeling and Simulation - Education and Professional

A model of engineering materials inspired by biological tissues

Directory of Open Access Journals (Sweden)

Holeček M.

2009-12-01

Full Text Available The perfect ability of living tissues to control and adapt their mechanical properties to varying external conditions may be an inspiration for designing engineering materials. An interesting example is the smooth muscle tissue since this "material" is able to change its global mechanical properties considerably by a subtle mechanism within individual muscle cells. Multi-scale continuum models may be useful in designing essentially simpler engineering materials having similar properties. As an illustration we present the model of an incompressible material whose microscopic structure is formed by flexible, soft but incompressible balls connected mutually by linear springs. This simple model, however, shows a nontrivial nonlinear behavior caused by the incompressibility of balls and is very sensitive on some microscopic parameters. It may elucidate the way by which "small" changes in biopolymer networks within individual muscular cells may control the stiffness of the biological tissue, which outlines a way of designing similar engineering materials. The 'balls and springs' material presents also prestress-induced stiffening and allows elucidating a contribution of extracellular fluids into the tissue’s viscous properties.

Interdisciplinary research and education at the biology-engineering-computer science interface: a perspective.

Science.gov (United States)

Tadmor, Brigitta; Tidor, Bruce

2005-09-01

Progress in the life sciences, including genome sequencing and high-throughput experimentation, offers an opportunity for understanding biology and medicine from a systems perspective. This 'new view', which complements the more traditional component-based approach, involves the integration of biological research with approaches from engineering disciplines and computer science. The result is more than a new set of technologies. Rather, it promises a fundamental reconceptualization of the life sciences based on the development of quantitative and predictive models to describe crucial processes. To achieve this change, learning communities are being formed at the interface of the life sciences, engineering and computer science. Through these communities, research and education will be integrated across disciplines and the challenges associated with multidisciplinary team-based science will be addressed.

Tracing organizing principles: Learning from the history of systems biology

DEFF Research Database (Denmark)

Green, Sara; Wolkenhauer, Olaf

2014-01-01

on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational......With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...

Geomagnetic Reversals during the Phanerozoic.

Science.gov (United States)

McElhinny, M W

1971-04-09

An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency.

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

Science.gov (United States)

Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-01-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

Science.gov (United States)

Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-03-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Jahnavi, S [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Saravanan, U [Department of Civil Engineering, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Arthi, N [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Bhuvaneshwar, G S [Department of Engineering Design, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Kumary, T V [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Rajan, S [Madras Medical Mission, Institute of Cardio-Vascular Diseases, Mogappair, Chennai, Tamil Nadu 600037 (India); Verma, R S, E-mail: vermars@iitm.ac.in [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India)

2017-04-01

Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44{sup +}, αSMA{sup +}, Vimentin{sup +} and CD105{sup −} human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. - Highlights: • We report detailed biological and mechanical investigations of a Bio-Hybrid scaffold. • Optimized polymer thickness yielded desired biological and mechanical properties. • Bio-Hybrid scaffold revealed hVIC proliferation with dense ECM deposition. • Biaxial testing indicated that Bio-Hybrid scaffolds are mechanically stronger than native valves. • Bio-Hybrid scaffold is a promising material for autologous valve tissue engineering.

PGASO: A synthetic biology tool for engineering a cellulolytic yeast

Directory of Open Access Journals (Sweden)

Chang Jui-Jen

2012-07-01

Full Text Available Abstract Background To achieve an economical cellulosic ethanol production, a host that can do both cellulosic saccharification and ethanol fermentation is desirable. However, to engineer a non-cellulolytic yeast to be such a host requires synthetic biology techniques to transform multiple enzyme genes into its genome. Results A technique, named Promoter-based Gene Assembly and Simultaneous Overexpression (PGASO, that employs overlapping oligonucleotides for recombinatorial assembly of gene cassettes with individual promoters, was developed. PGASO was applied to engineer Kluyveromycesmarxianus KY3, which is a thermo- and toxin-tolerant yeast. We obtained a recombinant strain, called KR5, that is capable of simultaneously expressing exoglucanase and endoglucanase (both of Trichodermareesei, a beta-glucosidase (from a cow rumen fungus, a neomycin phosphotransferase, and a green fluorescent protein. High transformation efficiency and accuracy were achieved as ~63% of the transformants was confirmed to be correct. KR5 can utilize beta-glycan, cellobiose or CMC as the sole carbon source for growth and can directly convert cellobiose and beta-glycan to ethanol. Conclusions This study provides the first example of multi-gene assembly in a single step in a yeast species other than Saccharomyces cerevisiae. We successfully engineered a yeast host with a five-gene cassette assembly and the new host is capable of co-expressing three types of cellulase genes. Our study shows that PGASO is an efficient tool for simultaneous expression of multiple enzymes in the kefir yeast KY3 and that KY3 can serve as a host for developing synthetic biology tools.

Biofuel production in Escherichia coli. The role of metabolic engineering and synthetic biology

Energy Technology Data Exchange (ETDEWEB)

Clomburg, James M. [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Gonzalez, Ramon [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Rice Univ., Houston, TX (United States). Dept. of Bioengineering

2010-03-15

The microbial production of biofuels is a promising avenue for the development of viable processes for the generation of fuels from sustainable resources. In order to become cost and energy effective, these processes must utilize organisms that can be optimized to efficiently produce candidate fuels from a variety of feedstocks. Escherichia coli has become a promising host organism for the microbial production of biofuels in part due to the ease at which this organism can be manipulated. Advancements in metabolic engineering and synthetic biology have led to the ability to efficiently engineer E. coli as a biocatalyst for the production of a wide variety of potential biofuels from several biomass constituents. This review focuses on recent efforts devoted to engineering E. coli for the production of biofuels, with emphasis on the key aspects of both the utilization of a variety of substrates as well as the synthesis of several promising biofuels. Strategies for the efficient utilization of carbohydrates, carbohydrate mixtures, and noncarbohydrate carbon sources will be discussed along with engineering efforts for the exploitation of both fermentative and nonfermentative pathways for the production of candidate biofuels such as alcohols and higher carbon biofuels derived from fatty acid and isoprenoid pathways. Continued advancements in metabolic engineering and synthetic biology will help improve not only the titers, yields, and productivities of biofuels discussed herein, but also increase the potential range of compounds that can be produced. (orig.)

A Survey of Automatic Protocol Reverse Engineering Approaches, Methods, and Tools on the Inputs and Outputs View

OpenAIRE

Baraka D. Sija; Young-Hoon Goo; Kyu-Seok Shim; Huru Hasanova; Myung-Sup Kim

2018-01-01

A network protocol defines rules that control communications between two or more machines on the Internet, whereas Automatic Protocol Reverse Engineering (APRE) defines the way of extracting the structure of a network protocol without accessing its specifications. Enough knowledge on undocumented protocols is essential for security purposes, network policy implementation, and management of network resources. This paper reviews and analyzes a total of 39 approaches, methods, and tools towards ...

Is synthetic biology mechanical biology?

Science.gov (United States)

Holm, Sune

2015-12-01

A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

Creating biological nanomaterials using synthetic biology

International Nuclear Information System (INIS)

Rice, MaryJoe K; Ruder, Warren C

2014-01-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

Creating biological nanomaterials using synthetic biology.

Science.gov (United States)

Rice, MaryJoe K; Ruder, Warren C

2014-02-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

Engineered matrices for skeletal muscle satellite cell engraftment and function.

Science.gov (United States)

Han, Woojin M; Jang, Young C; García, Andrés J

2017-07-01

Regeneration of traumatically injured skeletal muscles is severely limited. Moreover, the regenerative capacity of skeletal muscle declines with aging, further exacerbating the problem. Recent evidence supports that delivery of muscle satellite cells to the injured muscles enhances muscle regeneration and reverses features of aging, including reduction in muscle mass and regenerative capacity. However, direct delivery of satellite cells presents a challenge at a translational level due to inflammation and donor cell death, motivating the need to develop engineered matrices for muscle satellite cell delivery. This review will highlight important aspects of satellite cell and their niche biology in the context of muscle regeneration, and examine recent progresses in the development of engineered cell delivery matrices designed for skeletal muscle regeneration. Understanding the interactions of muscle satellite cells and their niche in both native and engineered systems is crucial to developing muscle pathology-specific cell- and biomaterial-based therapies. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

Science.gov (United States)

Cross, James H., II

1990-01-01

The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.

Science.gov (United States)

Pandey, Ramesh Prasad; Parajuli, Prakash; Koffas, Mattheos A G; Sohng, Jae Kyung

2016-01-01

In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described. Copyright © 2016 Elsevier Inc. All rights reserved.

Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

Directory of Open Access Journals (Sweden)

Ahmad Mohammad Abdel-Mawgoud

2018-03-01

Full Text Available Glycosylated lipids (GLs are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

Reverse engineering of wörner type drilling machine structure.

Science.gov (United States)

Wibowo, A.; Belly, I.; llhamsyah, R.; Indrawanto; Yuwana, Y.

2018-03-01

A product design needs to be modified based on the conditions of production facilities and existing resource capabilities without reducing the functional aspects of the product itself. This paper describes the reverse engineering process of the main structure of the wörner type drilling machine to obtain a machine structure design that can be made by resources with limited ability by using simple processes. Some structural, functional and the work mechanism analyzes have been performed to understand the function and role of each basic components. The process of dismantling of the drilling machine and measuring each of the basic components was performed to obtain sets of the geometry and size data of each component. The geometric model of each structure components and the machine assembly were built to facilitate the simulation process and machine performance analysis that refers to ISO standard of drilling machine. The tolerance stackup analysis also performed to determine the type and value of geometrical and dimensional tolerances, which could affect the ease of the components to be manufactured and assembled

Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

Energy Technology Data Exchange (ETDEWEB)

Madhavan, Aravind [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Rajiv Gandhi Centre for Biotechnology, Trivandrum (India); Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran, E-mail: sindhurgcb@gmail.com; Sukumaran, Rajeev K. [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Pandey, Ashok [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Center for Innovative and Applied Bioprocessing, Mohali, Punjab (India); Castro, Galliano Eulogio [Dpt. Ingeniería Química, Ambiental y de los Materiales Edificio, Universidad de Jaén, Jaén (Spain)

2017-04-25

The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

Directory of Open Access Journals (Sweden)

Raveendran Sindhu

2017-04-01

Full Text Available The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

International Nuclear Information System (INIS)

Madhavan, Aravind; Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran; Sukumaran, Rajeev K.; Pandey, Ashok; Castro, Galliano Eulogio

2017-01-01

The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

Science.gov (United States)

Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

2017-01-24

Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

Dental pulp stem cells. Biology and use for periodontal tissue engineering.

Science.gov (United States)

Ashri, Nahid Y; Ajlan, Sumaiah A; Aldahmash, Abdullah M

2015-12-01

Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors.

Political science. Reverse-engineering censorship in China: randomized experimentation and participant observation.

Science.gov (United States)

King, Gary; Pan, Jennifer; Roberts, Margaret E

2014-08-22

Existing research on the extensive Chinese censorship organization uses observational methods with well-known limitations. We conducted the first large-scale experimental study of censorship by creating accounts on numerous social media sites, randomly submitting different texts, and observing from a worldwide network of computers which texts were censored and which were not. We also supplemented interviews with confidential sources by creating our own social media site, contracting with Chinese firms to install the same censoring technologies as existing sites, and--with their software, documentation, and even customer support--reverse-engineering how it all works. Our results offer rigorous support for the recent hypothesis that criticisms of the state, its leaders, and their policies are published, whereas posts about real-world events with collective action potential are censored. Copyright © 2014, American Association for the Advancement of Science.

Synthetic biology and metabolic engineering for marine carotenoids: new opportunities and future prospects.

Science.gov (United States)

Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

2014-09-17

Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

Is nanotechnology the key to unravel and engineer biological processes?

Science.gov (United States)

Navarro, Melba; Planell, Josep A

2012-01-01

Regenerative medicine is an emerging field aiming to the development of new reparative strategies to treat degenerative diseases, injury, and trauma through developmental pathways in order to rebuild the architecture of the original injured organ and take over its functionality. Most of the processes and interactions involved in the regenerative process take place at subcellular scale. Nanotechnology provides the tools and technology not only to detect, to measure, or to image the interactions between the different biomolecules and biological entities, but also to control and guide the regenerative process. The relevance of nanotechnology for the development of regenerative medicine as well as an overview of the different tools that contribute to unravel and engineer biological systems are presented in this chapter. In addition, general data about the social impact and global investment in nanotechnology are provided.

Expanding the chemical palate of cells by combining systems biology and metabolic engineering.

Science.gov (United States)

Curran, Kathleen A; Alper, Hal S

2012-07-01

The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and specialty chemicals. Much of this rapid expansion in the field has been, in part, due to synergies and advances in the area of systems biology. Specifically, the availability of functional genomics, metabolomics and transcriptomics data has resulted in the potential to produce a wealth of new products, both natural and non-natural, in cellular factories. The sheer amount and diversity of this data however, means that uncovering and unlocking novel chemistries and insights is a non-obvious exercise. To address this issue, a number of computational tools and experimental approaches have been developed to help expedite the design process to create new cellular factories. This review will highlight many of the systems biology enabling technologies that have reduced the design cycle for engineered hosts, highlight major advances in the expanded diversity of products that can be synthesized, and conclude with future prospects in the field of metabolic engineering. Copyright © 2012 Elsevier Inc. All rights reserved.

Proceedings of the 8. Mediterranean Conference on Medical and Biological Engineering and Computing (Medicon `98)

Energy Technology Data Exchange (ETDEWEB)

Christofides, Stelios; Pattichis, Constantinos; Schizas, Christos; Keravnou-Papailiou, Elpida; Kaplanis, Prodromos; Spyros, Spyrou; Christodoulides, George; Theodoulou, Yiannis [eds.

1999-12-31

Medicon `98 is the eighth in the series of regional meetings of the International Federation of Medical and Biological Engineering (IFMBE) in the Mediterranean. The goal of Medicon `98 is to provide updated information on the state of the art on medical and biological engineering and computing. Medicon `98 was held in Lemesos, Cyprus, between 14-17 June, 1998. The full papers of the proceedings were published on CD and consisted of 190 invited and submitted papers. A book of abstracts was also published in paper form and was available to all the participants. Twenty seven papers fall within the scope of INIS and are dealing with Nuclear Medicine,Computerized Tomography, Radiology, Radiotherapy, Magnetic Resonance Imaging and Personnel Dosimetry (eds).

Proceedings of the 8. Mediterranean Conference on Medical and Biological Engineering and Computing (Medicon '98)

International Nuclear Information System (INIS)

Christofides, Stelios; Pattichis, Constantinos; Schizas, Christos; Keravnou-Papailiou, Elpida; Kaplanis, Prodromos; Spyros, Spyrou; Christodoulides, George; Theodoulou, Yiannis

1998-01-01

Medicon '98 is the eighth in the series of regional meetings of the International Federation of Medical and Biological Engineering (IFMBE) in the Mediterranean. The goal of Medicon '98 is to provide updated information on the state of the art on medical and biological engineering and computing. Medicon '98 was held in Lemesos, Cyprus, between 14-17 June, 1998. The full papers of the proceedings were published on CD and consisted of 190 invited and submitted papers. A book of abstracts was also published in paper form and was available to all the participants. Twenty seven papers fall within the scope of INIS and are dealing with Nuclear Medicine,Computerized Tomography, Radiology, Radiotherapy, Magnetic Resonance Imaging and Personnel Dosimetry (eds)

Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

Directory of Open Access Journals (Sweden)

Chonglong Wang

2014-09-01

Full Text Available Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

Science.gov (United States)

Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

2014-01-01

Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations. PMID:25233369

Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science.

Science.gov (United States)

Lenas, Petros; Moos, Malcolm; Luyten, Frank P

2009-12-01

The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has

Reverse Genetics Approaches for the Development of Influenza Vaccines

Science.gov (United States)

Nogales, Aitor; Martínez-Sobrido, Luis

2016-01-01

Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

Reverse engineering by design: using history to teach.

Science.gov (United States)

Fagette, Paul

2013-01-01

Engineering students rarely have an opportunity to delve into the historic antecedents of design in their craft, and this is especially true for biomedical devices. The teaching emphasis is always on the new, the innovative, and the future. Even so, over the last decade, I have coupled a research agenda with engineering special projects into a successful format that allows young biomedical engineering students to understand aspects of their history and learn the complexities of design. There is value in having knowledge of historic engineering achievements, not just for an appreciation of these accomplishments but also for understanding exactly how engineers and clinicians of the day executed their feats-in other words, how the design process works. Ultimately, this particular educational odyssey confirms that history and engineering education are not only compatible but mutually supportive.

Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels

Energy Technology Data Exchange (ETDEWEB)

Kuk Lee, Sung; Chou, Howard; Ham, Timothy S.; Soon Lee, Taek; Keasling, Jay D.

2009-12-02

The ability to generate microorganisms that can produce biofuels similar to petroleum-based transportation fuels would allow the use of existing engines and infrastructure and would save an enormous amount of capital required for replacing the current infrastructure to accommodate biofuels that have properties significantly different from petroleum-based fuels. Several groups have demonstrated the feasibility of manipulating microbes to produce molecules similar to petroleum-derived products, albeit at relatively low productivity (e.g. maximum butanol production is around 20 g/L). For cost-effective production of biofuels, the fuel-producing hosts and pathways must be engineered and optimized. Advances in metabolic engineering and synthetic biology will provide new tools for metabolic engineers to better understand how to rewire the cell in order to create the desired phenotypes for the production of economically viable biofuels.

Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

Science.gov (United States)

Liu, Ying; Deng, Wenbin

2016-05-01

With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

Synthetic constructs in/for the environment: managing the interplay between natural and engineered Biology.

Science.gov (United States)

Schmidt, Markus; de Lorenzo, Víctor

2012-07-16

The plausible release of deeply engineered or even entirely synthetic/artificial microorganisms raises the issue of their intentional (e.g. bioremediation) or accidental interaction with the Environment. Containment systems designed in the 1980s-1990s for limiting the spread of genetically engineered bacteria and their recombinant traits are still applicable to contemporary Synthetic Biology constructs. Yet, the ease of DNA synthesis and the uncertainty on how non-natural properties and strains could interplay with the existing biological word poses yet again the challenge of designing safe and efficacious firewalls to curtail possible interactions. Such barriers may include xeno-nucleic acids (XNAs) instead of DNA as information-bearing molecules, rewriting the genetic code to make it non-understandable by the existing gene expression machineries, and/or making growth dependent on xenobiotic chemicals. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

Science.gov (United States)

Lenas, Petros; Luyten, Frank P; Doblare, Manuel; Nicodemou-Lena, Eleni; Lanzara, Andreina Elena

2011-06-01

Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

Science.gov (United States)

Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

2008-02-19

Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

PREFACE: Nanobiology: from physics and engineering to biology

Science.gov (United States)

Nussinov, Ruth; Alemán, Carlos

2006-03-01

Biological systems are inherently nano in scale. Unlike nanotechnology, nanobiology is characterized by the interplay between physics, materials science, synthetic organic chemistry, engineering and biology. Nanobiology is a new discipline, with the potential of revolutionizing medicine: it combines the tools, ideas and materials of nanoscience and biology; it addresses biological problems that can be studied and solved by nanotechnology; it devises ways to construct molecular devices using biomacromolecules; and it attempts to build molecular machines utilizing concepts seen in nature. Its ultimate aim is to be able to predictably manipulate these, tailoring them to specified needs. Nanobiology targets biological systems and uses biomacromolecules. Hence, on the one hand, nanobiology is seemingly constrained in its scope as compared to general nanotechnology. Yet the amazing intricacy of biological systems, their complexity, and the richness of the shapes and properties provided by the biological polymers, enrich nanobiology. Targeting biological systems entails comprehension of how they work and the ability to use their components in design. From the physical standpoint, ultimately, if we are to understand biology we need to learn how to apply physical principles to figure out how these systems actually work. The goal of nanobiology is to assist in probing these systems at the appropriate length scale, heralding a new era in the biological, physical and chemical sciences. Biology is increasingly asking quantitative questions. Quantitation is essential if we are to understand how the cell works, and the details of its regulation. The physical sciences provide tools and strategies to obtain accurate measurements and simulate the information to allow comprehension of the processes. Nanobiology is at the interface of the physical and the biological sciences. Biology offers to the physical sciences fascinating problems, sophisticated systems and a rich repertoire of

Biological effects of radiation

International Nuclear Information System (INIS)

2013-01-01

This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

Building biological foundries for next-generation synthetic biology.

Science.gov (United States)

Chao, Ran; Yuan, YongBo; Zhao, HuiMin

2015-07-01

Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.

Slowly switching between environments facilitates reverse evolution in small populations

Science.gov (United States)

Tan, Longzhi; Gore, Jeff

2011-03-01

The rate at which a physical process occurs usually changes the behavior of a system. In thermodynamics, the reversibility of a process generally increases when it occurs at an infinitely slow rate. In biological evolution, adaptations to a new environment may be reversed by evolution in the ancestral environment. Such fluctuating environments are ubiquitous in nature, although how the rate of switching affects reverse evolution is unknown. Here we use a computational approach to quantify evolutionary reversibility as a function of the rate of switching between two environments. For small population sizes, which travel on landscapes as random walkers, we find that both genotypic and phenotypic reverse evolution increase at slow switching rates. However, slow switching of environments decreases evolutionary reversibility for a greedy walker, corresponding to large populations (extensive clonal interference). We conclude that the impact of the switching rate for biological evolution is more complicated than other common physical processes, and that a quantitative approach may yield significant insight into reverse evolution.

Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering.

Science.gov (United States)

Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S

2017-04-01

Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44 + , αSMA + , Vimentin + and CD105 - human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of hTERT-immortalized cells in tissue engineering

DEFF Research Database (Denmark)

Kassem, Moustapha; Abdallah, Basem; Yu, Zentao

2004-01-01

The use of human telomerase reverse transcriptase (hTERT)-immortalized cells in tissue engineering protocols is a potentially important application of telomere biology. Several human cell types have been created that overexpress the hTERT gene with enhanced telomerase activity, extended life span...... and maintained or even improved functional activities. Furthermore, some studies have employed the telomerized cells in tissue engineering protocols with very good results. However, high telomerase activity allows extensive cell proliferation that may be associated with genomic instability and risk for cell...... transformation. Thus, safety issues should be studied carefully before using the telomerized tissues in the clinic. Alternatively, the development of conditional or intermittent telomerase activation protocols is needed....

Biological variability in biomechanical engineering research: Significance and meta-analysis of current modeling practices.

Science.gov (United States)

Cook, Douglas; Julias, Margaret; Nauman, Eric

2014-04-11

Biological systems are characterized by high levels of variability, which can affect the results of biomechanical analyses. As a review of this topic, we first surveyed levels of variation in materials relevant to biomechanics, and compared these values to standard engineered materials. As expected, we found significantly higher levels of variation in biological materials. A meta-analysis was then performed based on thorough reviews of 60 research studies from the field of biomechanics to assess the methods and manner in which biological variation is currently handled in our field. The results of our meta-analysis revealed interesting trends in modeling practices, and suggest a need for more biomechanical studies that fully incorporate biological variation in biomechanical models and analyses. Finally, we provide some case study example of how biological variability may provide valuable insights or lead to surprising results. The purpose of this study is to promote the advancement of biomechanics research by encouraging broader treatment of biological variability in biomechanical modeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

Science.gov (United States)

Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

2017-12-05

The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

Insights gained from the reverse engineering of gene networks in keloid fibroblasts

Directory of Open Access Journals (Sweden)

Phan Toan

2011-05-01

Full Text Available Abstract Background Keloids are protrusive claw-like scars that have a propensity to recur even after surgery, and its molecular etiology remains elusive. The goal of reverse engineering is to infer gene networks from observational data, thus providing insight into the inner workings of a cell. However, most attempts at modeling biological networks have been done using simulated data. This study aims to highlight some of the issues involved in working with experimental data, and at the same time gain some insights into the transcriptional regulatory mechanism present in keloid fibroblasts. Methods Microarray data from our previous study was combined with microarray data obtained from the literature as well as new microarray data generated by our group. For the physical approach, we used the fREDUCE algorithm for correlating expression values to binding motifs. For the influence approach, we compared the Bayesian algorithm BANJO with the information theoretic method ARACNE in terms of performance in recovering known influence networks obtained from the KEGG database. In addition, we also compared the performance of different normalization methods as well as different types of gene networks. Results Using the physical approach, we found consensus sequences that were active in the keloid condition, as well as some sequences that were responsive to steroids, a commonly used treatment for keloids. From the influence approach, we found that BANJO was better at recovering the gene networks compared to ARACNE and that transcriptional networks were better suited for network recovery compared to cytokine-receptor interaction networks and intracellular signaling networks. We also found that the NFKB transcriptional network that was inferred from normal fibroblast data was more accurate compared to that inferred from keloid data, suggesting a more robust network in the keloid condition. Conclusions Consensus sequences that were found from this study are

Bacterial genome engineering and synthetic biology: combating pathogens.

Science.gov (United States)

Krishnamurthy, Malathy; Moore, Richard T; Rajamani, Sathish; Panchal, Rekha G

2016-11-04

The emergence and prevalence of multidrug resistant (MDR) pathogenic bacteria poses a serious threat to human and animal health globally. Nosocomial infections and common ailments such as pneumonia, wound, urinary tract, and bloodstream infections are becoming more challenging to treat due to the rapid spread of MDR pathogenic bacteria. According to recent reports by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), there is an unprecedented increase in the occurrence of MDR infections worldwide. The rise in these infections has generated an economic strain worldwide, prompting the WHO to endorse a global action plan to improve awareness and understanding of antimicrobial resistance. This health crisis necessitates an immediate action to target the underlying mechanisms of drug resistance in bacteria. The advent of new bacterial genome engineering and synthetic biology (SB) tools is providing promising diagnostic and treatment plans to monitor and treat widespread recalcitrant bacterial infections. Key advances in genetic engineering approaches can successfully aid in targeting and editing pathogenic bacterial genomes for understanding and mitigating drug resistance mechanisms. In this review, we discuss the application of specific genome engineering and SB methods such as recombineering, clustered regularly interspaced short palindromic repeats (CRISPR), and bacterial cell-cell signaling mechanisms for pathogen targeting. The utility of these tools in developing antibacterial strategies such as novel antibiotic production, phage therapy, diagnostics and vaccine production to name a few, are also highlighted. The prevalent use of antibiotics and the spread of MDR bacteria raise the prospect of a post-antibiotic era, which underscores the need for developing novel therapeutics to target MDR pathogens. The development of enabling SB technologies offers promising solutions to deliver safe and effective antibacterial therapies.

The bioartificial pancreas (BAP): Biological, chemical and engineering challenges.

Science.gov (United States)

Iacovacci, Veronica; Ricotti, Leonardo; Menciassi, Arianna; Dario, Paolo

2016-01-15

The bioartificial pancreas (BAP) represents a viable solution for the treatment of type 1 diabetes (T1D). By encapsulating pancreatic cells in a semipermeable membrane to allow nutrient, insulin and glucose exchange, the side effects produced by islets and whole organ transplantation-related immunosuppressive therapy can be circumvented. Several factors, mainly related to materials properties, capsule morphology and biological environment, play a key role in optimizing BAP systems. The BAP is an extremely complex delivery system for insulin. Despite considerable efforts, in some instances meeting with limited degree of success, a BAP capable of restoring physiological pancreas functions without the need for immunosuppressive drugs and of controlling blood glucose levels especially in large animal models and a few clinical trials, does not exist. The state of the art in terms of materials, fabrication techniques and cell sources, as well as the current status of commercial devices and clinical trials, are described in this overview from an interdisciplinary viewpoint. In addition, challenges to the creation of effective BAP systems are highlighted including future perspectives in terms of component integration from both a biological and an engineering viewpoint. Copyright © 2015 Elsevier Inc. All rights reserved.

Osmotic versus conventional membrane bioreactors integrated with reverse osmosis for water reuse: Biological stability, membrane fouling, and contaminant removal.

Science.gov (United States)

Luo, Wenhai; Phan, Hop V; Xie, Ming; Hai, Faisal I; Price, William E; Elimelech, Menachem; Nghiem, Long D

2017-02-01

This study systematically compares the performance of osmotic membrane bioreactor - reverse osmosis (OMBR-RO) and conventional membrane bioreactor - reverse osmosis (MBR-RO) for advanced wastewater treatment and water reuse. Both systems achieved effective removal of bulk organic matter and nutrients, and almost complete removal of all 31 trace organic contaminants investigated. They both could produce high quality water suitable for recycling applications. During OMBR-RO operation, salinity build-up in the bioreactor reduced the water flux and negatively impacted the system biological treatment by altering biomass characteristics and microbial community structure. In addition, the elevated salinity also increased soluble microbial products and extracellular polymeric substances in the mixed liquor, which induced fouling of the forward osmosis (FO) membrane. Nevertheless, microbial analysis indicated that salinity stress resulted in the development of halotolerant bacteria, consequently sustaining biodegradation in the OMBR system. By contrast, biological performance was relatively stable throughout conventional MBR-RO operation. Compared to conventional MBR-RO, the FO process effectively prevented foulants from permeating into the draw solution, thereby significantly reducing fouling of the downstream RO membrane in OMBR-RO operation. Accumulation of organic matter, including humic- and protein-like substances, as well as inorganic salts in the MBR effluent resulted in severe RO membrane fouling in conventional MBR-RO operation. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Proceedings of the Joint Conference of Australasian College of Physical Scientists and Engineers in Medicine and IEAust College of Biomedical Engineers; Asia/Pacific Region of the IEEE Engineering in Medicine and Biology Society

International Nuclear Information System (INIS)

1996-01-01

This is a celebration of the centenary of Rontgen''s discovery of Xrays. It is also the 50th anniversary of the first hospital physicist appointment in New Zealand. The historical element of the programme will complement the emphasis on current applications of the physical and engineering sciences to medicine and an anticipation of future developments. For the first time the Australasian College of Physical Scientists and Engineers in Medicine, together with the IEAust College of Biomedical Engineers, are joined by the Asia/Pacific Region of the IEEE Engineering in Medicine and Biology Society to make this a truly international conference. The proceedings include many papers on radiology and radiotherapy

An Integrated Reverse Engineering Approach for Accuracy Control of Free-Form Objects

Directory of Open Access Journals (Sweden)

Pathak Vimal Kumar

2016-12-01

Full Text Available Computer-aided tools help in shortening and eradicating numerous repetitive tasks that reduces the gap between digital model and actual product. Use of these tools assists in realizing free-form objects such as custom fit products as described by a stringent interaction with the human body. Development of such a model presents a challenging situation for reverse engineering (RE which is not analogous with the requirement for generating simple geometric models. Hence, an alternating way of producing more accurate three-dimensional models is proposed. For creating accurate 3D models, point clouds are processed through filtering, segmentation, mesh smoothing and surface generation. These processes help in converting the initial unorganized point data into a 3D digital model and simultaneously influence the quality of model. This study provides an optimum balance for the best accuracy obtainable with maximum allowable deviation to lessen computer handling and processing time. A realistic non trivial case study of free-form prosthetic socket is considered. The accuracy obtained for the developed model is acceptable for the use in medical applications and FEM analysis.

Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

Science.gov (United States)

Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

2017-08-17

Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals

DEFF Research Database (Denmark)

Jullesson, David; David, Florian; Pfleger, Brian

2015-01-01

Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played...... chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes....... an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine...

A proposal to enhance Engineering education in biology and Medicine by following the legacy of René Favaloro.

Science.gov (United States)

Armentano, Ricardo L; Cardelino, Juan; Wray, Sandra; Cymberknop, Leandro J; Kun, Luis

2015-01-01

The synergy amongst Engineering, Medicine and Biology evolves as fast as these disciplines. We propose to articulate these specialties based on the premise that new professionals must face different situations or crisis due to the so-called islands of excellence. René Favaloro focused his work and struggles against poverty, since malnutrition and environmental degradation may increase the propensity to cardiovascular diseases. Doctor Favaloro has dedicated, throughout his career, a considerable amount of time to prepare and qualify a research group, aware of the importance that an adequate working environment has over the final results. He created a team of young students, engineers, medical doctors, physicists, mathematicians and other specialists. He centered his attention on human resources, in order to disseminate his latest advances in Biology, Medicine and Engineering. We are revising the programs of biomedical engineering education and the application of new pedagogic paradigms, where critical thinking is the key: a holistic challenge that consists of a new way of learning, innovating, communicating and shearing, with a creative attitude that represents quality of perception.

Delineation and interpretation of gene networks towards their effect in cellular physiology- a reverse engineering approach for the identification of critical molecular players, through the use of ontologies.

Science.gov (United States)

Moutselos, K; Maglogiannis, I; Chatziioannou, A

2010-01-01

Exploiting ontologies, provides clues regarding the involvement of certain molecular processes in the cellular phenotypic manifestation. However, identifying individual molecular actors (genes, proteins, etc.) for targeted biological validation in a generic, prioritized, fashion, based in objective measures of their effects in the cellular physiology, remains a challenge. In this work, a new meta-analysis algorithm is proposed for the holistic interpretation of the information captured in -omic experiments, that is showcased in a transcriptomic, dynamic, DNA microarray dataset, which examines the effect of mastic oil treatment in Lewis lung carcinoma cells. Through the use of the Gene Ontology this algorithm relates genes to specific cellular pathways and vice versa in order to further reverse engineer the critical role of specific genes, starting from the results of various statistical enrichment analyses. The algorithm is able to discriminate candidate hub-genes, implying critical biochemical cross-talk. Moreover, performance measures of the algorithm are derived, when evaluated with respect to the differential expression gene list of the dataset.

Engineering and physics of high-power-density, compact, reversed-field-pinch fusion reactors

International Nuclear Information System (INIS)

Najmabadi, F.; Conn, R.W.; Krakowski, R.A.; Schultz, K.R.; Steiner, D.

1989-01-01

The technical feasibility and key developmental issues of compact, high-power-density Reversed-Field-Pinch (RFP) reactors are the primary results of the TITAN RFP reactor study. Two design approaches emerged, TITAN-I and TITAN-II, both of which are steady-state, DT-burning, circa 1000 MWe power reactors. The TITAN designs are physically compact and have a high neutron wall loading of 18 MW m 2 . Detailed analyses indicate that: a) each design is technically feasible; b) attractive features of compact RFP reactors can be realized without sacrificing the safety and environmental potential of fusion; and c) major features of this particular embodiment of the RFP reactor are retained in a design window of neutron wall loading ranging from 10 to 20 MW/m 2 . A major product of the TITAN study is the identification and quantification of major engineering and physics requirements for this class of RFP reactors. These findings are the focus of this paper. (author). 26 refs.; 4 figs.; 1 tab

[Computer aided design for fixed partial denture framework based on reverse engineering technology].

Science.gov (United States)

Sun, Yu-chun; Lü, Pei-jun; Wang, Yong

2006-03-01

To explore a computer aided design (CAD) route for the framework of domestic fixed partial denture (FPD) and confirm the suitable method of 3-D CAD. The working area of a dentition model was scanned with a 3-D mechanical scanner. Using the reverse engineering (RE) software, margin and border curves were extracted and several reference curves were created to ensure the dimension and location of pontic framework that was taken from the standard database. The shoulder parts of the retainers were created after axial surfaces constructed. The connecting areas, axial line and curving surface of the framework connector were finally created. The framework of a three-unit FPD was designed with RE technology, which showed smooth surfaces and continuous contours. The design route is practical. The result of this study is significant in theory and practice, which will provide a reference for establishing the computer aided design/computer aided manufacture (CAD/CAM) system of domestic FPD.

Chemical respiratory allergy: Reverse engineering an adverse outcome pathway

International Nuclear Information System (INIS)

Kimber, Ian; Dearman, Rebecca J.; Basketter, David A.; Boverhof, Darrell R.

2014-01-01

Allergic sensitisation of the respiratory tract by chemicals is associated with rhinitis and asthma and remains an important occupational health issue. Although less than 80 chemicals have been confirmed as respiratory allergens the adverse health effects can be serious, and in rare instances can be fatal, and there are, in addition, related socioeconomic issues. The challenges that chemical respiratory allergy pose for toxicologists are substantial. No validated methods are available for hazard identification and characterisation, and this is due in large part to the fact that there remains considerable uncertainty and debate about the mechanisms through which sensitisation of the respiratory tract is acquired. Despite that uncertainty, there is a need to establish some common understanding of the key events and processes that are involved in respiratory sensitisation to chemicals and that might in turn provide the foundations for novel approaches to safety assessment. In recent years the concept of adverse outcome pathways (AOP) has gained some considerable interest among the toxicology community as a basis for outlining the key steps leading to an adverse health outcome, while also providing a framework for focusing future research, and for developing alternative paradigms for hazard characterisation. Here we explore application of the same general principles to an examination of the induction by chemicals of respiratory sensitisation. In this instance, however, we have chosen to adopt a reverse engineering approach and to model a possible AOP for chemical respiratory allergy working backwards from the elicitation of adverse health effects to the cellular and molecular mechanisms that are implicated in the acquisition of sensitisation

Laser marking as a result of applying reverse engineering

Science.gov (United States)

Mihalache, Andrei; Nagîţ, Gheorghe; Rîpanu, Marius Ionuţ; Slǎtineanu, Laurenţiu; Dodun, Oana; Coteaţǎ, Margareta

2018-05-01

The elaboration of a modern manufacturing technology needs a certain quantum of information concerning the part to be obtained. When it is necessary to elaborate the technology for an existing object, such an information could be ensured by using the principles specific to the reverse engineering. Essentially, in the case of this method, the analysis of the surfaces and of other characteristics of the part must offer enough information for the elaboration of the part manufacturing technology. On the other hand, it is known that the laser marking is a processing method able to ensure the transfer of various inscriptions or drawings on a part. Sometimes, the laser marking could be based on the analysis of an existing object, whose image could be used to generate the same object or an improved object. There are many groups of factors able to affect the results of applying the laser marking process. A theoretical analysis was proposed to show that the heights of triangles obtained by means of a CNC marking equipment depend on the width of the line generated by the laser spot on the workpiece surface. An experimental research was thought and materialized to highlight the influence exerted by the line with and the angle of lines intersections on the accuracy of the marking process. By mathematical processing of the experimental results, empirical mathematical models were determined. The power type model and the graphical representation elaborated on the base of this model offered an image concerning the influences exerted by the considered input factors on the marking process accuracy.

Cuckoo Search Algorithm with Lévy Flights for Global-Support Parametric Surface Approximation in Reverse Engineering

Directory of Open Access Journals (Sweden)

Andrés Iglesias

2018-03-01

Full Text Available This paper concerns several important topics of the Symmetry journal, namely, computer-aided design, computational geometry, computer graphics, visualization, and pattern recognition. We also take advantage of the symmetric structure of the tensor-product surfaces, where the parametric variables u and v play a symmetric role in shape reconstruction. In this paper we address the general problem of global-support parametric surface approximation from clouds of data points for reverse engineering applications. Given a set of measured data points, the approximation is formulated as a nonlinear continuous least-squares optimization problem. Then, a recent metaheuristics called Cuckoo Search Algorithm (CSA is applied to compute all relevant free variables of this minimization problem (namely, the data parameters and the surface poles. The method includes the iterative generation of new solutions by using the Lévy flights to promote the diversity of solutions and prevent stagnation. A critical advantage of this method is its simplicity: the CSA requires only two parameters, many fewer than any other metaheuristic approach, so the parameter tuning becomes a very easy task. The method is also simple to understand and easy to implement. Our approach has been applied to a benchmark of three illustrative sets of noisy data points corresponding to surfaces exhibiting several challenging features. Our experimental results show that the method performs very well even for the cases of noisy and unorganized data points. Therefore, the method can be directly used for real-world applications for reverse engineering without further pre/post-processing. Comparative work with the most classical mathematical techniques for this problem as well as a recent modification of the CSA called Improved CSA (ICSA is also reported. Two nonparametric statistical tests show that our method outperforms the classical mathematical techniques and provides equivalent results to ICSA

An Interdisciplinary Approach for Biology, Technology, Engineering and Mathematics (BTEM to Enhance 21st Century Skills in Malaysia.

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Lee Chuo Hiong

2015-07-01

Full Text Available An interdisciplinary approach for Biology, Technology, Engineering and Mathematics (BTEM is suggested to develop 21st century skills in the Malaysian context. BTEM allows students to master biological knowledge and at the same time to be adroit in other sub discipline skills. Students master factual knowledge of biology and skills of the 21st century simultaneously. The two main teaching and learning strategies applied in BTEM are problem-based learning and inquiry-based learning. Students are exposed to real world problems that require them to undergo inquiry processes to discover the inventive solutions. The content knowledge of biology adheres to the Malaysian Integrated Curriculum for Secondary Schools. The essence of engineering is inventive problem solving. Incorporation of information communication technologies in teaching and learning will be able to fulfil the needs of the current Net Generation. Mathematics plays an important role as computational tools, especially in analysing data. The highlighted 21st century skills in BTEM include digital literacy, inventive thinking, effective communication, high productivity, and spiritual and noble values.

Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications.

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Bober, Josef R; Beisel, Chase L; Nair, Nikhil U

2018-03-12

An increasing number of studies have strongly correlated the composition of the human microbiota with many human health conditions and, in several cases, have shown that manipulating the microbiota directly affects health. These insights have generated significant interest in engineering indigenous microbiota community members and nonresident probiotic bacteria as biotic diagnostics and therapeutics that can probe and improve human health. In this review, we discuss recent advances in synthetic biology to engineer commensal and probiotic lactic acid bacteria, bifidobacteria, and Bacteroides for these purposes, and we provide our perspective on the future potential of these technologies. 277 Expected final online publication date for the Annual Review of Biomedical Engineering Volume 20 is June 4, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

Science.gov (United States)

Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

2015-01-01

Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals.

Science.gov (United States)

Jullesson, David; David, Florian; Pfleger, Brian; Nielsen, Jens

2015-11-15

Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Principle and realization of segmenting contour series algorithm in reverse engineering based on X-ray computerized tomography

International Nuclear Information System (INIS)

Wang Yanfang; Liu Li; Yan Yonglian; Shan Baoci; Tang Xiaowei

2007-01-01

A new algorithm of segmenting contour series of images is presented, which can achieve three dimension reconstruction with parametric recognition in Reverse Engineering based on X-ray CT. First, in order to get the nested relationship between contours, a method of a certain angle ray is used. Second, for realizing the contour location in one slice, another approach is presented to generate the contour tree by scanning the relevant vector only once. Last, a judge algorithm is put forward to accomplish the contour match between slices by adopting the qualitative and quantitative properties. The example shows that this algorithm can segment contour series of CT parts rapidly and precisely. (authors)

Models for synthetic biology.

Science.gov (United States)

Kaznessis, Yiannis N

2007-11-06

Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

Molecular Cloning Designer Simulator (MCDS: All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects

Directory of Open Access Journals (Sweden)

Zhenyu Shi

2016-12-01

Full Text Available Molecular Cloning Designer Simulator (MCDS is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1 it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2 it can perform a user-defined workflow of cloning steps in a single execution of the software; (3 it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4 it includes experimental information to conveniently guide wet lab work; and (5 it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com. Keywords: BioCAD, Genetic engineering software, Molecular cloning software, Synthetic biology, Workflow simulation and management

Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology.

Science.gov (United States)

Dvořák, Pavel; Nikel, Pablo I; Damborský, Jiří; de Lorenzo, Víctor

2017-11-15

Elimination or mitigation of the toxic effects of chemical waste released to the environment by industrial and urban activities relies largely on the catalytic activities of microorganisms-specifically bacteria. Given their capacity to evolve rapidly, they have the biochemical power to tackle a large number of molecules mobilized from their geological repositories through human action (e.g., hydrocarbons, heavy metals) or generated through chemical synthesis (e.g., xenobiotic compounds). Whereas naturally occurring microbes already have considerable ability to remove many environmental pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow revisiting the same environmental pollution challenges through fresh and far more powerful approaches. The focus on contaminated sites and chemicals has been broadened by the phenomenal problems of anthropogenic emissions of greenhouse gases and the accumulation of plastic waste on a global scale. In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering workflow. Copyright © 2017 Elsevier Inc. All rights reserved.

X-ray diffraction and infrared spectroscopy analyses on the crystallinity of engineered biological hydroxyapatite for medical application

Science.gov (United States)

Poralan, G. M., Jr.; Gambe, J. E.; Alcantara, E. M.; Vequizo, R. M.

2015-06-01

Biological hydroxyapatite (BHAp) derived from thermally-treated fish bones was successfully produced. However, the obtained biological HAp was amorphous and thus making it unfavorable for medical application. Consequently, this research exploits and engineers the crystallinity of BHAp powders by addition of CaCO3 and investigates its degree of crystallinity using XRD and IR spectroscopy. On XRD, the HAp powders with [Ca]/[P] ratios 1.42, 1.46, 1.61 and 1.93 have degree of crystallinity equal to 58.08, 72.13, 85.79, 75.85% and crystal size equal to 0.67, 0.74, 0.75, 0.72 nm, respectively. The degree of crystallinity and crystal size of the obtained calcium deficient biological HAp powders increase as their [Ca]/[P] ratio approaches the stoichiometric ratio by addition of CaCO3 as source of Ca2+ ions. These results show the possibility of engineering the crystallinity and crystal size of biological HAp by addition of CaCO3. Moreover, the splitting factor of PO4 vibration matches the result with % crystallinity on XRD. Also, the area of phosphate-substitution site of PO4 vibration shows linear relationship (R2 = 0.994) with crystal size calculated from XRD. It is worth noting that the crystallinity of the biological HAp with [Ca]/[P] ratios 1.42 and 1.48 fall near the range 60-70% for highly resorbable HAp used in the medical application.

Paradigms for biologically inspired design

DEFF Research Database (Denmark)

Lenau, T. A.; Metzea, A.-L.; Hesselberg, T.

2018-01-01

engineering, medical engineering, nanotechnology, photonics,environmental protection and agriculture. However, a major obstacle for the wider use of biologically inspired design isthe knowledge barrier that exist between the application engineers that have insight into how to design suitable productsand......Biologically inspired design is attracting increasing interest since it offers access to a huge biological repository of wellproven design principles that can be used for developing new and innovative products. Biological phenomena can inspireproduct innovation in as diverse areas as mechanical...... the biologists with detailed knowledge and experience in understanding how biological organisms function in theirenvironment. The biologically inspired design process can therefore be approached using different design paradigmsdepending on the dominant opportunities, challenges and knowledge characteristics...

Biologi og/eller engineering?

DEFF Research Database (Denmark)

Daugbjerg, Peer

2018-01-01

Engineering i skolen er en anvendelsesorienteret og problemløsende undervisning, hvor eleverne lærer at udvikle konkrete løsninger på praktiske problemer. I elevernes arbejde indgår faglig viden og teknologi...

Informing via Research: Methods, Challenges and Success when Using a Multi-Disciplinary Team and Reverse Engineering Analysis Processes to Answer a 200 Year Old Question

Directory of Open Access Journals (Sweden)

Melinda H. Connor

2014-10-01

Full Text Available The goal of this study was to develop the foundation for the creation of a 21st century spiritual which could be used to mitigate the effects of stress and violence. Using a multi-disciplinary team and basing the work in the music of the antebellum Negro Spiritual (a group of 6000 works, reverse engineering, extensive use of engineering principles and utilization of existing databases was done to aid in the analysis of the neurological and physiological impact of the musical form and development of an applicable theory.

Rabi model as a quantum coherent heat engine: From quantum biology to superconducting circuits

Science.gov (United States)

Altintas, Ferdi; Hardal, Ali Ü. C.; Müstecaplıoǧlu, Özgür E.

2015-02-01

We propose a multilevel quantum heat engine with a working medium described by a generalized Rabi model which consists of a two-level system coupled to a single-mode bosonic field. The model is constructed to be a continuum limit of a quantum biological description of light-harvesting complexes so that it can amplify quantum coherence by a mechanism which is a quantum analog of classical Huygens clocks. The engine operates in a quantum Otto cycle where the working medium is coupled to classical heat baths in the isochoric processes of the four-stroke cycle, while either the coupling strength or the resonance frequency is changed in the adiabatic stages. We found that such an engine can produce work with an efficiency close to the Carnot bound when it operates at low temperatures and in the ultrastrong-coupling regime. The interplay of the effects of quantum coherence and quantum correlations on the engine performance is discussed in terms of second-order coherence, quantum mutual information, and the logarithmic negativity of entanglement. We point out that the proposed quantum Otto engine can be implemented experimentally with modern circuit quantum electrodynamic systems where flux qubits can be coupled ultrastrongly to superconducting transmission-line resonators.

Understanding Biological Regulation Through Synthetic Biology.

Science.gov (United States)

Bashor, Caleb J; Collins, James J

2018-03-16

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Building a Better Microreactor: Enzyme Catalysis in AOT/Bile Salt Reversed Micelles

National Research Council Canada - National Science Library

McGown, Linda

2001-01-01

.... We have shown that trihydroxy bile salts modify the interfacial properties of AOT reversed micelles, thereby affecting the reversed micellar structure, the biological activity of entrapped enzymes...

Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.

Science.gov (United States)

Deddens, Janine C; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W; Buijsrogge, Marc; Doevendans, Pieter A; Khademhosseini, Ali; Sluijter, Joost P G

2017-02-01

Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A systems biology approach to transcription factor binding site prediction.

Directory of Open Access Journals (Sweden)

Xiang Zhou

2010-03-01

Full Text Available The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates.We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data.Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct-interaction detection and TFBS-discovery accuracy. We estimated the accuracy

Engineered reversal of drug resistance in cancer cells--metastases suppressor factors as change agents.

Science.gov (United States)

Yadav, Vinod Kumar; Kumar, Akinchan; Mann, Anita; Aggarwal, Suruchi; Kumar, Maneesh; Roy, Sumitabho Deb; Pore, Subrata Kumar; Banerjee, Rajkumar; Mahesh Kumar, Jerald; Thakur, Ram Krishna; Chowdhury, Shantanu

2014-01-01

Building molecular correlates of drug resistance in cancer and exploiting them for therapeutic intervention remains a pressing clinical need. To identify factors that impact drug resistance herein we built a model that couples inherent cell-based response toward drugs with transcriptomes of resistant/sensitive cells. To test this model, we focused on a group of genes called metastasis suppressor genes (MSGs) that influence aggressiveness and metastatic potential of cancers. Interestingly, modeling of 84 000 drug response transcriptome combinations predicted multiple MSGs to be associated with resistance of different cell types and drugs. As a case study, on inducing MSG levels in a drug resistant breast cancer line resistance to anticancer drugs caerulomycin, camptothecin and topotecan decreased by more than 50-60%, in both culture conditions and also in tumors generated in mice, in contrast to control un-induced cells. To our knowledge, this is the first demonstration of engineered reversal of drug resistance in cancer cells based on a model that exploits inherent cellular response profiles.

Designing synthetic biology.

Science.gov (United States)

Agapakis, Christina M

2014-03-21

Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

Reconstructing Causal Biological Networks through Active Learning.

Directory of Open Access Journals (Sweden)

Hyunghoon Cho

Full Text Available Reverse-engineering of biological networks is a central problem in systems biology. The use of intervention data, such as gene knockouts or knockdowns, is typically used for teasing apart causal relationships among genes. Under time or resource constraints, one needs to carefully choose which intervention experiments to carry out. Previous approaches for selecting most informative interventions have largely been focused on discrete Bayesian networks. However, continuous Bayesian networks are of great practical interest, especially in the study of complex biological systems and their quantitative properties. In this work, we present an efficient, information-theoretic active learning algorithm for Gaussian Bayesian networks (GBNs, which serve as important models for gene regulatory networks. In addition to providing linear-algebraic insights unique to GBNs, leading to significant runtime improvements, we demonstrate the effectiveness of our method on data simulated with GBNs and the DREAM4 network inference challenge data sets. Our method generally leads to faster recovery of underlying network structure and faster convergence to final distribution of confidence scores over candidate graph structures using the full data, in comparison to random selection of intervention experiments.

Plant synthetic biology.

Science.gov (United States)

Liu, Wusheng; Stewart, C Neal

2015-05-01

Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Time reversibility, computer simulation, algorithms, chaos

CERN Document Server

Hoover, William Graham

2012-01-01

A small army of physicists, chemists, mathematicians, and engineers has joined forces to attack a classic problem, the "reversibility paradox", with modern tools. This book describes their work from the perspective of computer simulation, emphasizing the author's approach to the problem of understanding the compatibility, and even inevitability, of the irreversible second law of thermodynamics with an underlying time-reversible mechanics. Computer simulation has made it possible to probe reversibility from a variety of directions and "chaos theory" or "nonlinear dynamics" has supplied a useful vocabulary and a set of concepts, which allow a fuller explanation of irreversibility than that available to Boltzmann or to Green, Kubo and Onsager. Clear illustration of concepts is emphasized throughout, and reinforced with a glossary of technical terms from the specialized fields which have been combined here to focus on a common theme. The book begins with a discussion, contrasting the idealized reversibility of ba...

Engineering controllable bidirectional molecular motors based on myosin

Science.gov (United States)

Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

2012-04-01

Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering.

Science.gov (United States)

Hadd, Andrew; Perona, John J

2014-12-19

We have taken a rational approach to redesigning the amino acid binding and aminoacyl-tRNA pairing specificities of bacterial glutaminyl-tRNA synthetase. The four-stage engineering incorporates generalizable design principles and improves the pairing efficiency of noncognate glutamate with tRNA(Gln) by over 10(5)-fold compared to the wild-type enzyme. Better optimized designs of the protein-RNA complex include substantial reengineering of the globular core region of the tRNA, demonstrating a role for specific tRNA nucleotides in specifying the identity of the genetically encoded amino acid. Principles emerging from this engineering effort open new prospects for combining rational and genetic selection approaches to design novel aminoacyl-tRNA synthetases that ligate noncanonical amino acids onto tRNAs. This will facilitate reconstruction of the cellular translation apparatus for applications in synthetic biology.

Engineering a palette of eukaryotic chromoproteins for bacterial synthetic biology.

Science.gov (United States)

Liljeruhm, Josefine; Funk, Saskia K; Tietscher, Sandra; Edlund, Anders D; Jamal, Sabri; Wistrand-Yuen, Pikkei; Dyrhage, Karl; Gynnå, Arvid; Ivermark, Katarina; Lövgren, Jessica; Törnblom, Viktor; Virtanen, Anders; Lundin, Erik R; Wistrand-Yuen, Erik; Forster, Anthony C

2018-01-01

Coral reefs are colored by eukaryotic chromoproteins (CPs) that are homologous to green fluorescent protein. CPs differ from fluorescent proteins (FPs) by intensely absorbing visible light to give strong colors in ambient light. This endows CPs with certain advantages over FPs, such as instrument-free detection uncomplicated by ultra-violet light damage or background fluorescence, efficient Förster resonance energy transfer (FRET) quenching, and photoacoustic imaging. Thus, CPs have found utility as genetic markers and in teaching, and are attractive for potential cell biosensor applications in the field. Most near-term applications of CPs require expression in a different domain of life: bacteria. However, it is unclear which of the eukaryotic CP genes might be suitable and how best to assay them. Here, taking advantage of codon optimization programs in 12 cases, we engineered 14 CP sequences (meffRed, eforRed, asPink, spisPink, scOrange, fwYellow, amilGFP, amajLime, cjBlue, meffBlue, aeBlue, amilCP, tsPurple and gfasPurple) into a palette of Escherichia coli BioBrick plasmids. BioBricks comply with synthetic biology's most widely used, simplified, cloning standard. Differences in color intensities, maturation times and fitness costs of expression were compared under the same conditions, and visible readout of gene expression was quantitated. A surprisingly large variation in cellular fitness costs was found, resulting in loss of color in some overnight liquid cultures of certain high-copy-plasmid-borne CPs, and cautioning the use of multiple CPs as markers in competition assays. We solved these two problems by integrating pairs of these genes into the chromosome and by engineering versions of the same CP with very different colors. Availability of 14 engineered CP genes compared in E. coli , together with chromosomal mutants suitable for competition assays, should simplify and expand CP study and applications. There was no single plasmid-borne CP that combined

Numerical Prediction of the Influence of Thrust Reverser on Aeroengine's Aerodynamic Stability

Science.gov (United States)

Zhiqiang, Wang; Xigang, Shen; Jun, Hu; Xiang, Gao; Liping, Liu

2017-11-01

A numerical method was developed to predict the aerodynamic stability of a high bypass ratio turbofan engine, at the landing stage of a large transport aircraft, when the thrust reverser was deployed. 3D CFD simulation and 2D aeroengine aerodynamic stability analysis code were performed in this work, the former is to achieve distortion coefficient for the analysis of engine stability. The 3D CFD simulation was divided into two steps, the single engine calculation and the integrated aircraft and engine calculation. Results of the CFD simulation show that with the decreasing of relative wind Mach number, the engine inlet will suffer more severe flow distortion. The total pressure and total temperature distortion coefficients at the inlet of the engines were obtained from the results of the numerical simulation. Then an aeroengine aerodynamic stability analysis program was used to quantitatively analyze the aerodynamic stability of the high bypass ratio turbofan engine. The results of the stability analysis show that the engine can work stably, when the reverser flow is re-ingested. But the anti-distortion ability of the booster is weaker than that of the fan and high pressure compressor. It is a weak link of engine stability.

Applications of Engineered DNA-Binding Molecules Such as TAL Proteins and the CRISPR/Cas System in Biology Research

Directory of Open Access Journals (Sweden)

Toshitsugu Fujita

2015-09-01

Full Text Available Engineered DNA-binding molecules such as transcription activator-like effector (TAL or TALE proteins and the clustered regularly interspaced short palindromic repeats (CRISPR and CRISPR-associated proteins (Cas (CRISPR/Cas system have been used extensively for genome editing in cells of various types and species. The sequence-specific DNA-binding activities of these engineered DNA-binding molecules can also be utilized for other purposes, such as transcriptional activation, transcriptional repression, chromatin modification, visualization of genomic regions, and isolation of chromatin in a locus-specific manner. In this review, we describe applications of these engineered DNA-binding molecules for biological purposes other than genome editing.

Tissue engineering and surgery: from translational studies to human trials

Directory of Open Access Journals (Sweden)

Vranckx Jan Jeroen

2017-06-01

Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

Hidden Randomness between Fitness Landscapes Limits Reverse Evolution

Science.gov (United States)

Tan, Longzhi; Serene, Stephen; Xiao Chao, Hui; Gore, Jeff

2012-02-01

Natural populations must constantly adapt to the ever-changing environment. A fundamental question in evolutionary biology is whether adaptations can be reversed by returning the population to its ancestral environment. Traditionally, reverse evolution is defined as restoring an ancestral phenotype (physical characteristics such as body size), and the classic Dollo's Law has hypothesized the impossibility of reversing complex adaptations. However, this ``law'' remains ambiguous unless reverse evolution can be studied at the level of genotypes (the underlying genome sequence). We measured the fitness landscapes of a bacterial antibiotic-resistance gene and analyzed the reversibility of evolution as a global, statistical feature of the landscapes. In both experiments and simulations, we find that an adaptation's reversibility declines as the number of mutations it involves increases, suggesting a probabilistic form of Dollo's Law at the molecular level. We also show computationally that slowly switching between environments facilitates reverse evolution in small populations, where clonal interference is negligible or moderate. This is an analogy to thermodynamics, where the reversibility of a physical process is maximized when conditions are modified infinitely slowly.

Informing biological design by integration of systems and synthetic biology.

Science.gov (United States)

Smolke, Christina D; Silver, Pamela A

2011-03-18

Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.

A design concept of parallel elasticity extracted from biological muscles for engineered actuators.

Science.gov (United States)

Chen, Jie; Jin, Hongzhe; Iida, Fumiya; Zhao, Jie

2016-08-23

Series elastic actuation that takes inspiration from biological muscle-tendon units has been extensively studied and used to address the challenges (e.g. energy efficiency, robustness) existing in purely stiff robots. However, there also exists another form of passive property in biological actuation, parallel elasticity within muscles themselves, and our knowledge of it is limited: for example, there is still no general design strategy for the elasticity profile. When we look at nature, on the other hand, there seems a universal agreement in biological systems: experimental evidence has suggested that a concave-upward elasticity behaviour is exhibited within the muscles of animals. Seeking to draw possible design clues for elasticity in parallel with actuators, we use a simplified joint model to investigate the mechanisms behind this biologically universal preference of muscles. Actuation of the model is identified from general biological joints and further reduced with a specific focus on muscle elasticity aspects, for the sake of easy implementation. By examining various elasticity scenarios, one without elasticity and three with elasticity of different profiles, we find that parallel elasticity generally exerts contradictory influences on energy efficiency and disturbance rejection, due to the mechanical impedance shift thus caused. The trade-off analysis between them also reveals that concave parallel elasticity is able to achieve a more advantageous balance than linear and convex ones. It is expected that the results could contribute to our further understanding of muscle elasticity and provide a theoretical guideline on how to properly design parallel elasticity behaviours for engineering systems such as artificial actuators and robotic joints.

Automation of reverse engineering process in aircraft modeling and related optimization problems

Science.gov (United States)

Li, W.; Swetits, J.

1994-01-01

During the year of 1994, the engineering problems in aircraft modeling were studied. The initial concern was to obtain a surface model with desirable geometric characteristics. Much of the effort during the first half of the year was to find an efficient way of solving a computationally difficult optimization model. Since the smoothing technique in the proposal 'Surface Modeling and Optimization Studies of Aerodynamic Configurations' requires solutions of a sequence of large-scale quadratic programming problems, it is important to design algorithms that can solve each quadratic program in a few interactions. This research led to three papers by Dr. W. Li, which were submitted to SIAM Journal on Optimization and Mathematical Programming. Two of these papers have been accepted for publication. Even though significant progress has been made during this phase of research and computation times was reduced from 30 min. to 2 min. for a sample problem, it was not good enough for on-line processing of digitized data points. After discussion with Dr. Robert E. Smith Jr., it was decided not to enforce shape constraints in order in order to simplify the model. As a consequence, P. Dierckx's nonparametric spline fitting approach was adopted, where one has only one control parameter for the fitting process - the error tolerance. At the same time the surface modeling software developed by Imageware was tested. Research indicated a substantially improved fitting of digitalized data points can be achieved if a proper parameterization of the spline surface is chosen. A winning strategy is to incorporate Dierckx's surface fitting with a natural parameterization for aircraft parts. The report consists of 4 chapters. Chapter 1 provides an overview of reverse engineering related to aircraft modeling and some preliminary findings of the effort in the second half of the year. Chapters 2-4 are the research results by Dr. W. Li on penalty functions and conjugate gradient methods for

Thermal Stabilization of Biologics with Photoresponsive Hydrogels.

Science.gov (United States)

Sridhar, Balaji V; Janczy, John R; Hatlevik, Øyvind; Wolfson, Gabriel; Anseth, Kristi S; Tibbitt, Mark W

2018-03-12

Modern medicine, biological research, and clinical diagnostics depend on the reliable supply and storage of complex biomolecules. However, biomolecules are inherently susceptible to thermal stress and the global distribution of value-added biologics, including vaccines, biotherapeutics, and Research Use Only (RUO) proteins, requires an integrated cold chain from point of manufacture to point of use. To mitigate reliance on the cold chain, formulations have been engineered to protect biologics from thermal stress, including materials-based strategies that impart thermal stability via direct encapsulation of the molecule. While direct encapsulation has demonstrated pronounced stabilization of proteins and complex biological fluids, no solution offers thermal stability while enabling facile and on-demand release from the encapsulating material, a critical feature for broad use. Here we show that direct encapsulation within synthetic, photoresponsive hydrogels protected biologics from thermal stress and afforded user-defined release at the point of use. The poly(ethylene glycol) (PEG)-based hydrogel was formed via a bioorthogonal, click reaction in the presence of biologics without impact on biologic activity. Cleavage of the installed photolabile moiety enabled subsequent dissolution of the network with light and release of the encapsulated biologic. Hydrogel encapsulation improved stability for encapsulated enzymes commonly used in molecular biology (β-galactosidase, alkaline phosphatase, and T4 DNA ligase) following thermal stress. β-galactosidase and alkaline phosphatase were stabilized for 4 weeks at temperatures up to 60 °C, and for 60 min at 85 °C for alkaline phosphatase. T4 DNA ligase, which loses activity rapidly at moderately elevated temperatures, was protected during thermal stress of 40 °C for 24 h and 60 °C for 30 min. These data demonstrate a general method to employ reversible polymer networks as robust excipients for thermal stability of complex

Introduction to tissue engineering and application for cartilage engineering.

Science.gov (United States)

de Isla, N; Huseltein, C; Jessel, N; Pinzano, A; Decot, V; Magdalou, J; Bensoussan, D; Stoltz, J-F

2010-01-01

Tissue engineering is a multidisciplinary field that applies the principles of engineering, life sciences, cell and molecular biology toward the development of biological substitutes that restore, maintain, and improve tissue function. In Western Countries, tissues or cells management for clinical uses is a medical activity governed by different laws. Three general components are involved in tissue engineering: (1) reparative cells that can form a functional matrix; (2) an appropriate scaffold for transplantation and support; and (3) bioreactive molecules, such as cytokines and growth factors that will support and choreograph formation of the desired tissue. These three components may be used individually or in combination to regenerate organs or tissues. Thus the growing development of tissue engineering needs to solve four main problems: cells, engineering development, grafting and safety studies.

Suitability of a PLCL fibrous scaffold for soft tissue engineering applications: A combined biological and mechanical characterisation.

Science.gov (United States)

Laurent, Cédric P; Vaquette, Cédryck; Liu, Xing; Schmitt, Jean-François; Rahouadj, Rachid

2018-04-01

Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.

Reversible Carnot cycle outside a black hole

International Nuclear Information System (INIS)

Xi-Hao, Deng; Si-Jie, Gao

2009-01-01

A Carnot cycle outside a Schwarzschild black hole is investigated in detail. We propose a reversible Carnot cycle with a black hole being the cold reservoir. In our model, a Carnot engine operates between a hot reservoir with temperature T 1 and a black hole with Hawking temperature T H . By naturally extending the ordinary Carnot cycle to the black hole system, we show that the thermal efficiency for a reversible process can reach the maximal efficiency 1 – T H /T 1 . Consequently, black holes can be used to determine the thermodynamic temperature by means of the Carnot cycle. The role of the atmosphere around the black hole is discussed. We show that the thermal atmosphere provides a necessary mechanism to make the process reversible. (general)

Reversible Control of Anisotropic Electrical Conductivity using Colloidal Microfluidic Networks

National Research Council Canada - National Science Library

Beskok, Ali; Bevan, Michael; Lagoudas, Dimitris; Ounaies, Zoubeida; Bahukudumbi, Pradipkumar; Everett, William

2007-01-01

This research addresses the tunable assembly of reversible colloidal structures within microfluidic networks to engineer multifunctional materials that exhibit a wide range of electrical properties...

Industrial systems biology and its impact on synthetic biology of yeast cell factories

DEFF Research Database (Denmark)

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-01-01

Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools......, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex...... regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal...

Reversals and collisions optimize protein exchange in bacterial swarms

Energy Technology Data Exchange (ETDEWEB)

Amiri, Aboutaleb; Harvey, Cameron; Buchmann, Amy; Christley, Scott; Shrout, Joshua D.; Aranson, Igor S.; Alber, Mark

2017-03-01

Swarming groups of bacteria coordinate their behavior by self-organizing as a population to move over surfaces in search of nutrients and optimal niches for colonization. Many open questions remain about the cues used by swarming bacteria to achieve this self-organization. While chemical cue signaling known as quorum sensing is well-described, swarming bacteria often act and coordinate on time scales that could not be achieved via these extracellular quorum sensing cues. Here, cell-cell contact-dependent protein exchange is explored as amechanism of intercellular signaling for the bacterium Myxococcus xanthus. A detailed biologically calibrated computational model is used to study how M. xanthus optimizes the connection rate between cells and maximizes the spread of an extracellular protein within the population. The maximum rate of protein spreading is observed for cells that reverse direction optimally for swarming. Cells that reverse too slowly or too fast fail to spread extracellular protein efficiently. In particular, a specific range of cell reversal frequencies was observed to maximize the cell-cell connection rate and minimize the time of protein spreading. Furthermore, our findings suggest that predesigned motion reversal can be employed to enhance the collective behavior of biological synthetic active systems.

An Analytical Reverse Engineering of IELTS Listening Tasks for a Construct Model

Directory of Open Access Journals (Sweden)

Masood Khalili Sabet

2017-10-01

Full Text Available The study reported here was concerned with the issue of reverse engineering of language test items as it relates to the identification of the language constructs underlying listening tasks of LELTS test. In this regard, the IELTS examination papers, from IELTS 1 to IELTS 10 were compiled as a corpus for the analysis. Tasks were analyzed using a taxonomic frame work adopted from Moore, Morton and price (2012, that was originally adapted from Weir and Urquhart (1998, with a focus on two dimensions of difference: level of engagement, referring to the level of text with which a listener required to engage in order to respond to a task (local vs. global; type of engagement referring to the way (or ways  listeners expected to engage with a text in order to process the material to respond to a task (literal vs. interpretative. Overall, the analysis found evidences of bottom up processing underlying most IELTS listening tasks. The majority of tasks were identified to have a ‘local-literal’ configuration on their orientation, demanding primarily a basic understanding of relatively small textual units of the material. The results of the study were used to suggest the practical implications for the four groups of the people involved in the IELTS educational contexts: participants; teachers; material preparation experts, and curriculum designers.

The TITAN reversed-field-pinch fusion reactor study

International Nuclear Information System (INIS)

1990-01-01

This paper on titan plasma engineering contains papers on the following topics: reversed-field pinch as a fusion reactor; parametric systems studies; magnetics; burning-plasma simulations; plasma transient operations; current drive; and physics issues for compact RFP reactors

Quantum biological information theory

CERN Document Server

Djordjevic, Ivan B

2016-01-01

This book is a self-contained, tutorial-based introduction to quantum information theory and quantum biology. It serves as a single-source reference to the topic for researchers in bioengineering, communications engineering, electrical engineering, applied mathematics, biology, computer science, and physics. The book provides all the essential principles of the quantum biological information theory required to describe the quantum information transfer from DNA to proteins, the sources of genetic noise and genetic errors as well as their effects. Integrates quantum information and quantum biology concepts; Assumes only knowledge of basic concepts of vector algebra at undergraduate level; Provides a thorough introduction to basic concepts of quantum information processing, quantum information theory, and quantum biology; Includes in-depth discussion of the quantum biological channel modelling, quantum biological channel capacity calculation, quantum models of aging, quantum models of evolution, quantum models o...

Engineering controllable bidirectional molecular motors based on myosin

Science.gov (United States)

Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

2012-01-01

Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells1, and have potential applications in molecular detection and diagnostic devices2,3. Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in living cells, and yield optimized device components for complex tasks such as molecular sorting and directed assembly3. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions4,5 and other signals6. Here we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies7–11 and guided by a structural model12 for the redirected power stroke of myosin VI, we constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our general strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should enable spatiotemporal control over a range of motor properties including processivity, stride size13, and branchpoint turning14. PMID:22343382

Chemical Engineering in the "BIO" World.

Science.gov (United States)

Chiarappa, Gianluca; Grassi, Mario; Abrami, Michela; Abbiati, Roberto Andrea; Barba, Anna Angela; Boisen, Anja; Brucato, Valerio; Ghersi, Giulio; Caccavo, Diego; Cascone, Sara; Caserta, Sergio; Elvassore, Nicola; Giomo, Monica; Guido, Stefano; Lamberti, Gaetano; Larobina, Domenico; Manca, Davide; Marizza, Paolo; Tomaiuolo, Giovanna; Grassi, Gabriele

2017-01-01

Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advanced 3D tools used in reverse engineering and ray tracing simulation of phased array inspection of turbine components with complex geometry

International Nuclear Information System (INIS)

Daks, W.; Kovacshazy, C.; Mair, D.; Ciorau, P.

2002-01-01

This paper outlines the practical aspects of reverse engineering and the integration of multiple pieces of software (Drafting, CNC Machining, Ray Tracing, Inspection Simulation Scenario and Phased Array UT Analysis), in order to inspect turbine components comprised of complex geometry. The CNC software, Mastercam, and design software, CADKEY/FastSURF, were used to validate the phased-array automated and manual inspection of blade root, rotor steeples and disk-blade rim attachment. The integration of a 3D part in the software engine, Imagine 3D and SimScan, as well as Tomoview analysis (specimen feature) is based on CADKEY Developer Kit - IGES/SAT file format. A generic Ray Tracing simulation for multi-probe beam was integrated into Imagine 3D. Representative examples of reference blocks and mock-ups, UT simulation and phased-array data comparison are presented. (author)

Biological performance of titania containing phosphate-based glasses for bone tissue engineering applications

International Nuclear Information System (INIS)

Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Knowles, Jonathan Campbell

2014-01-01

The interplay between glass chemistry, structure, degradation kinetics, and biological activity provides flexibility for the development of scaffolds with highly specific cellular response. The aim of this study was therefore to investigate the role of titania inclusion into the phosphate-based glass on its ability to stimulate osteoblast-like human osteosarcoma (HOS) cells to adhere, proliferate and differentiate. In depth morphological and biochemical characterisation was performed on HOS cells cultured on the surface of glass discs. Cell proliferation was also studied in the presence of the glass extract. Cell differentiation, through osteoblast phenotype genes, alkaline phosphatase (ALP) activity and osteocalcin production, was carried out using normal or osteogenic media. Both Thermanox® and titania free glass were used as controls. The data demonstrated that titania inclusion provides desired cytocompatible surface that supported initial cell attachment, sustained viability, and increased cell proliferation similar or significantly higher than Thermanox®. The modified glasses regulated osteoblastic cell differentiation as detected by osteoblast phenotype gene transcription and upregulated ALP and osteocalcin expression. Using osteogenic media had no significant effect on ALP activity and osteocalcin expression. Therefore, titania modified phosphate glasses may have future use as bone tissue engineering scaffolds. - Highlights: • This study investigated the role of titania on the biological response of phosphate glasses. • Incorporation of titania improved HOS cell attachment, viability and proliferation. • Titania modified glasses regulated osteoblastic cell differentiation. • Using osteogenic media had no significant effect on cell differentiation. • Titania modified glasses may have future use as bone tissue engineering scaffolds

Diffusion properties of active particles with directional reversal

International Nuclear Information System (INIS)

Großmann, R; Bär, M; Peruani, F

2016-01-01

The diffusion properties of self-propelled particles which move at constant speed and, in addition, reverse their direction of motion repeatedly are investigated. The internal dynamics of particles triggering these reversal processes is modeled by a stochastic clock. The velocity correlation function as well as the mean squared displacement is investigated and, furthermore, a general expression for the diffusion coefficient for self-propelled particles with directional reversal is derived. Our analysis reveals the existence of an optimal, finite rotational noise amplitude which maximizes the diffusion coefficient. We comment on the relevance of these results with regard to biological systems and suggest further experiments in this context. (paper)

Development of a tetrameric streptavidin mutein with reversible biotin binding capability: engineering a mobile loop as an exit door for biotin.

Directory of Open Access Journals (Sweden)

Valerie J O'Sullivan

Full Text Available A novel form of tetrameric streptavidin has been engineered to have reversible biotin binding capability. In wild-type streptavidin, loop(3-4 functions as a lid for the entry and exit of biotin. When biotin is bound, interactions between biotin and key residues in loop(3-4 keep this lid in the closed state. In the engineered mutein, a second biotin exit door is created by changing the amino acid sequence of loop(7-8. This door is mobile even in the presence of the bound biotin and can facilitate the release of biotin from the mutein. Since loop(7-8 is involved in subunit interactions, alteration of this loop in the engineered mutein results in an 11° rotation between the two dimers in reference to wild-type streptavidin. The tetrameric state of the engineered mutein is stabilized by a H127C mutation, which leads to the formation of inter-subunit disulfide bonds. The biotin binding kinetic parameters (k(off of 4.28×10(-4 s(-1 and K(d of 1.9×10(-8 M make this engineered mutein a superb affinity agent for the purification of biotinylated biomolecules. Affinity matrices can be regenerated using gentle procedures, and regenerated matrices can be reused at least ten times without any observable reduction in binding capacity. With the combination of both the engineered mutein and wild-type streptavidin, biotinylated biomolecules can easily be affinity purified to high purity and immobilized to desirable platforms without any leakage concerns. Other potential biotechnological applications, such as development of an automated high-throughput protein purification system, are feasible.

Development of a Tetrameric Streptavidin Mutein with Reversible Biotin Binding Capability: Engineering a Mobile Loop as an Exit Door for Biotin

Science.gov (United States)

O'Sullivan, Valerie J.; Barrette-Ng, Isabelle; Hommema, Eric; Hermanson, Greg T.; Schofield, Mark; Wu, Sau-Ching; Honetschlaeger, Claudia; Ng, Kenneth K.-S.; Wong, Sui-Lam

2012-01-01

A novel form of tetrameric streptavidin has been engineered to have reversible biotin binding capability. In wild-type streptavidin, loop3–4 functions as a lid for the entry and exit of biotin. When biotin is bound, interactions between biotin and key residues in loop3–4 keep this lid in the closed state. In the engineered mutein, a second biotin exit door is created by changing the amino acid sequence of loop7–8. This door is mobile even in the presence of the bound biotin and can facilitate the release of biotin from the mutein. Since loop7–8 is involved in subunit interactions, alteration of this loop in the engineered mutein results in an 11° rotation between the two dimers in reference to wild-type streptavidin. The tetrameric state of the engineered mutein is stabilized by a H127C mutation, which leads to the formation of inter-subunit disulfide bonds. The biotin binding kinetic parameters (koff of 4.28×10−4 s−1 and Kd of 1.9×10−8 M) make this engineered mutein a superb affinity agent for the purification of biotinylated biomolecules. Affinity matrices can be regenerated using gentle procedures, and regenerated matrices can be reused at least ten times without any observable reduction in binding capacity. With the combination of both the engineered mutein and wild-type streptavidin, biotinylated biomolecules can easily be affinity purified to high purity and immobilized to desirable platforms without any leakage concerns. Other potential biotechnological applications, such as development of an automated high-throughput protein purification system, are feasible. PMID:22536357

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

Science.gov (United States)

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

BioTCM-SE: a semantic search engine for the information retrieval of modern biology and traditional Chinese medicine.

Science.gov (United States)

Chen, Xi; Chen, Huajun; Bi, Xuan; Gu, Peiqin; Chen, Jiaoyan; Wu, Zhaohui

2014-01-01

Understanding the functional mechanisms of the complex biological system as a whole is drawing more and more attention in global health care management. Traditional Chinese Medicine (TCM), essentially different from Western Medicine (WM), is gaining increasing attention due to its emphasis on individual wellness and natural herbal medicine, which satisfies the goal of integrative medicine. However, with the explosive growth of biomedical data on the Web, biomedical researchers are now confronted with the problem of large-scale data analysis and data query. Besides that, biomedical data also has a wide coverage which usually comes from multiple heterogeneous data sources and has different taxonomies, making it hard to integrate and query the big biomedical data. Embedded with domain knowledge from different disciplines all regarding human biological systems, the heterogeneous data repositories are implicitly connected by human expert knowledge. Traditional search engines cannot provide accurate and comprehensive search results for the semantically associated knowledge since they only support keywords-based searches. In this paper, we present BioTCM-SE, a semantic search engine for the information retrieval of modern biology and TCM, which provides biologists with a comprehensive and accurate associated knowledge query platform to greatly facilitate the implicit knowledge discovery between WM and TCM.

BioTCM-SE: A Semantic Search Engine for the Information Retrieval of Modern Biology and Traditional Chinese Medicine

Directory of Open Access Journals (Sweden)

Xi Chen

2014-01-01

Full Text Available Understanding the functional mechanisms of the complex biological system as a whole is drawing more and more attention in global health care management. Traditional Chinese Medicine (TCM, essentially different from Western Medicine (WM, is gaining increasing attention due to its emphasis on individual wellness and natural herbal medicine, which satisfies the goal of integrative medicine. However, with the explosive growth of biomedical data on the Web, biomedical researchers are now confronted with the problem of large-scale data analysis and data query. Besides that, biomedical data also has a wide coverage which usually comes from multiple heterogeneous data sources and has different taxonomies, making it hard to integrate and query the big biomedical data. Embedded with domain knowledge from different disciplines all regarding human biological systems, the heterogeneous data repositories are implicitly connected by human expert knowledge. Traditional search engines cannot provide accurate and comprehensive search results for the semantically associated knowledge since they only support keywords-based searches. In this paper, we present BioTCM-SE, a semantic search engine for the information retrieval of modern biology and TCM, which provides biologists with a comprehensive and accurate associated knowledge query platform to greatly facilitate the implicit knowledge discovery between WM and TCM.

A data-driven approach to reverse engineering customer engagement models: towards functional constructs.

Science.gov (United States)

de Vries, Natalie Jane; Carlson, Jamie; Moscato, Pablo

2014-01-01

Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The 'communities' of questionnaire items that emerge from our community detection method form possible 'functional constructs' inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such 'functional constructs' suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling.

A data-driven approach to reverse engineering customer engagement models: towards functional constructs.

Directory of Open Access Journals (Sweden)

Natalie Jane de Vries

Full Text Available Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The 'communities' of questionnaire items that emerge from our community detection method form possible 'functional constructs' inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such 'functional constructs' suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling.

Reversibility and retrievability in geologic disposal of radioactive waste

International Nuclear Information System (INIS)

2001-01-01

Reversibility of decisions is an important consideration in the step-wise decision-making process that is foreseen for engineered geologic disposal of radioactive waste. The implications of favouring retrievability of the waste within disposal strategies and the methods to implement it are also being considered by NEA Member countries. This report reviews the concepts of reversibility and retrievability as they may apply to the planning and development of engineered geologic repositories. The concepts span technical, policy and ethical issues, and it is important that a broad understanding is developed of their value and implications. Furthermore, improved comprehension and communication of these issues will clarify the value of flexible, step-wise decision making in repository development programmes and may help to generate a climate conducive to the further progress of such programmes. (author)

A new class of potential chloroquine-resistance reversal agents for Plasmodia: syntheses and biological evaluation of 1-(3'-diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines.

Science.gov (United States)

Batra, S; Srivastava, P; Roy, K; Pandey, V C; Bhaduri, A P

2000-09-07

1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

Integrating biological redesign: where synthetic biology came from and where it needs to go.

Science.gov (United States)

Way, Jeffrey C; Collins, James J; Keasling, Jay D; Silver, Pamela A

2014-03-27

Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

A Representation-Theoretic Approach to Reversible Computation with Applications

DEFF Research Database (Denmark)

Maniotis, Andreas Milton

Reversible computing is a sub-discipline of computer science that helps to understand the foundations of the interplay between physics, algebra, and logic in the context of computation. Its subjects of study are computational devices and abstract models of computation that satisfy the constraint ......, there is still no uniform and consistent theory that is general in the sense of giving a model-independent account to the field....... of information conservation. Such machine models, which are known as reversible models of computation, have been examined both from a theoretical perspective and from an engineering perspective. While a bundle of many isolated successful findings and applications concerning reversible computing exists...

A proposal to establish an international network in molecular microbiology and genetic engineering for scientific cooperation and prevention of misuse of biological sciences in the framework of science for peace

International Nuclear Information System (INIS)

Becker, Y.

1998-01-01

The conference on 'Science and Technology for Construction of Peace' which was organized by the Landau Network Coordination Center and A. Volta Center for Scientific Culture dealt with conversion of military and technological capacities into sustainable civilian application. The ideas regarding the conversion of nuclear warheads into nuclear energy for civilian-use led to the idea that the extension of this trend of thought to molecular biology and genetic engineering, will be a useful contribution to Science for Peace. This idea of developing a Cooperation Network in Molecular Biology and Genetic Engineering that will function parallel to and with the Landau Network Coordination in the 'A. Volta' Center was discussed in the Second International Symposium on Science for Peace, Jerusalem, January 1997. It is the reason for the inclusion of the biological aspects in the deliberations of our Forum. It is hoped that the establishment of an international network in molecular biology and genetic engineering, similar to the Landau Network in physics, will support and achieve the decommissioning of biological weapons. Such a network in microbiology and genetic engineering will contribute to the elimination of biological weapons and to contributions to Science for Peace and to Culture of Peace activities of UNESCO. (author)

A fluorogenic molecular nanoprobe with an engineered internal environment for sensitive and selective detection of biological hydrogen sulfide.

Science.gov (United States)

Kim, Myung; Seo, Young Hun; Kim, Youngsun; Heo, Jeongyun; Jang, Woo-Dong; Sim, Sang Jun; Kim, Sehoon

2017-02-14

A nanoreactor approach based on the amphiphilic assembly of various molecules offers a chance to finely engineer the internal reaction medium to enable highly selective and sensitive detection of H 2 S in biological media, being useful for microscopic imaging of cellular processes and in vitro diagnostics with blood samples.

Reverse Engineering Tone-Deafness: Disrupting Pitch-Matching by Creating Temporary Dysfunctions in the Auditory-Motor Network

Directory of Open Access Journals (Sweden)

Anja Hohmann

2018-01-01

Full Text Available Perceiving and producing vocal sounds are important functions of the auditory-motor system and are fundamental to communication. Prior studies have identified a network of brain regions involved in pitch production, specifically pitch matching. Here we reverse engineer the function of the auditory perception-production network by targeting specific cortical regions (e.g., right and left posterior superior temporal (pSTG and posterior inferior frontal gyri (pIFG with cathodal transcranial direct current stimulation (tDCS—commonly found to decrease excitability in the underlying cortical region—allowing us to causally test the role of particular nodes in this network. Performance on a pitch-matching task was determined before and after 20 min of cathodal stimulation. Acoustic analyses of pitch productions showed impaired accuracy after cathodal stimulation to the left pIFG and the right pSTG in comparison to sham stimulation. Both regions share particular roles in the feedback and feedforward motor control of pitched vocal production with a differential hemispheric dominance.

Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism

Science.gov (United States)

Kim, Eunkyoung; Panzella, Lucia; Micillo, Raffaella; Bentley, William E.; Napolitano, Alessandra; Payne, Gregory F.

2015-01-01

Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin’s pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin’s redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism. PMID:26669666

Macromolecular cell surface engineering for accelerated and reversible cellular aggregation.

OpenAIRE

Amaral, A. J.; Pasparakis, G.

2015-01-01

We report the synthesis of two simple copolymers that induce rapid cell aggregation within minutes in a fully reversible manner. The polymers can act as self-supporting "cellular glues" or as "drivers" of 3D cell spheroids/aggregates formation at minute concentrations.

Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course

Science.gov (United States)

Dymond, Jessica S.; Scheifele, Lisa Z.; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S.; Boeke, Jef D.

2009-01-01

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ∼750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science. PMID:19015540

Quantum engine efficiency bound beyond the second law of thermodynamics.

Science.gov (United States)

Niedenzu, Wolfgang; Mukherjee, Victor; Ghosh, Arnab; Kofman, Abraham G; Kurizki, Gershon

2018-01-11

According to the second law, the efficiency of cyclic heat engines is limited by the Carnot bound that is attained by engines that operate between two thermal baths under the reversibility condition whereby the total entropy does not increase. Quantum engines operating between a thermal and a squeezed-thermal bath have been shown to surpass this bound. Yet, their maximum efficiency cannot be determined by the reversibility condition, which may yield an unachievable efficiency bound above unity. Here we identify the fraction of the exchanged energy between a quantum system and a bath that necessarily causes an entropy change and derive an inequality for this change. This inequality reveals an efficiency bound for quantum engines energised by a non-thermal bath. This bound does not imply reversibility, unless the two baths are thermal. It cannot be solely deduced from the laws of thermodynamics.

Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges.

Science.gov (United States)

Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta

2009-08-01

Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.

Thrust reverser design studies for an over-the-wing STOL transport

Science.gov (United States)

Ammer, R. C.; Sowers, H. D.

1977-01-01

Aerodynamic and acoustics analytical studies were conducted to evaluate three thrust reverser designs for potential use on commercial over-the-wing STOL transports. The concepts were: (1) integral D nozzle/target reverser, (2) integral D nozzle/top arc cascade reverser, and (3) post exit target reverser integral with wing. Aerodynamic flowpaths and kinematic arrangements for each concept were established to provide a 50% thrust reversal capability. Analytical aircraft stopping distance/noise trade studies conducted concurrently with flow path design showed that these high efficiency reverser concepts are employed at substantially reduced power settings to meet noise goals of 100 PNdB on a 152.4 m sideline and still meet 609.6 m landing runway length requirements. From an overall installation standpoint, only the integral D nozzle/target reverser concept was found to penalize nacelle cruise performance; for this concept a larger nacelle diameter was required to match engine cycle effective area demand in reverse thrust.

Toward design-based engineering of industrial microbes.

Science.gov (United States)

Tyo, Keith E J; Kocharin, Kanokarn; Nielsen, Jens

2010-06-01

Engineering industrial microbes has been hampered by incomplete knowledge of cell biology. Thus an iterative engineering cycle of modeling, implementation, and analysis has been used to increase knowledge of the underlying biology while achieving engineering goals. Recent advances in Systems Biology technologies have drastically improved the amount of information that can be collected in each iteration. As well, Synthetic Biology tools are melding modeling and molecular implementation. These advances promise to move microbial engineering from the iterative approach to a design-oriented paradigm, similar to electrical circuits and architectural design. Genome-scale metabolic models, new tools for controlling expression, and integrated -omics analysis are described as key contributors in moving the field toward Design-based Engineering. Copyright 2010 Elsevier Ltd. All rights reserved.

Modularization of genetic elements promotes synthetic metabolic engineering.

Science.gov (United States)

Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

2015-11-15

In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Liquid-liquid extraction by reversed micelles in biotechnological processes

Directory of Open Access Journals (Sweden)

Kilikian B. V.

2000-01-01

Full Text Available In biotechnology there is a need for new purification and concentration processes for biologically active compounds such as proteins, enzymes, nucleic acids, or cells that combine a high selectivity and biocompatibility with an easy scale-up. A liquid-liquid extraction with a reversed micellar phase might serve these purposes owing to its capacity to solubilize specific biomolecules from dilute aqueous solutions such as fermentation and cell culture media. Reversed micelles are aggregates of surfactant molecules containing an inner core of water molecules, dispersed in a continuous organic solvent medium. These reversed micelles are capable of selectively solubilizing polar compounds in an apolar solvent. This review gives an overview of liquid-liquid extraction by reversed micelles for a better understanding of this process.

Thermal noise engines

OpenAIRE

Kish, Laszlo B.

2010-01-01

Electrical heat engines driven by the Johnson-Nyquist noise of resistors are introduced. They utilize Coulomb's law and the fluctuation-dissipation theorem of statistical physics that is the reverse phenomenon of heat dissipation in a resistor. No steams, gases, liquids, photons, combustion, phase transition, or exhaust/pollution are present here. In these engines, instead of heat reservoirs, cylinders, pistons and valves, resistors, capacitors and switches are the building elements. For the ...

Synthetic biology: programming cells for biomedical applications.

Science.gov (United States)

Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

2012-01-01

The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

Promoting convergence: The integrated graduate program in physical and engineering biology at Yale University, a new model for graduate education.

Science.gov (United States)

Noble, Dorottya B; Mochrie, Simon G J; O'Hern, Corey S; Pollard, Thomas D; Regan, Lynne

2016-11-12

In 2008, we established the Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) at Yale University. Our goal was to create a comprehensive graduate program to train a new generation of scientists who possess a sophisticated understanding of biology and who are capable of applying physical and quantitative methodologies to solve biological problems. Here we describe the framework of the training program, report on its effectiveness, and also share the insights we gained during its development and implementation. The program features co-teaching by faculty with complementary specializations, student peer learning, and novel hands-on courses that facilitate the seamless blending of interdisciplinary research and teaching. It also incorporates enrichment activities to improve communication skills, engage students in science outreach, and foster a cohesive program cohort, all of which promote the development of transferable skills applicable in a variety of careers. The curriculum of the graduate program is integrated with the curricular requirements of several Ph.D.-granting home programs in the physical, engineering, and biological sciences. Moreover, the wide-ranging recruiting activities of the IGPPEB serve to enhance the quality and diversity of students entering graduate school at Yale. We also discuss some of the challenges we encountered in establishing and optimizing the program, and describe the institution-level changes that were catalyzed by the introduction of the new graduate program. The goal of this article is to serve as both an inspiration and as a practical "how to" manual for those who seek to establish similar programs at their own institutions. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):537-549, 2016. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

Enzyme and metabolic engineering for the production of novel biopolymers: crossover of biological and chemical processes.

Science.gov (United States)

Matsumoto, Ken'ichiro; Taguchi, Seiichi

2013-12-01

The development of synthetic biology has transformed microbes into useful factories for producing valuable polymers and/or their precursors from renewable biomass. Recent progress at the interface of chemistry and biology has enabled the production of a variety of new biopolymers with properties that substantially differ from their petroleum-derived counterparts. This review touches on recent trials and achievements in the field of biopolymer synthesis, including chemo-enzymatically synthesized aliphatic polyesters, wholly biosynthesized lactate-based polyesters, polyhydroxyalkanoates and other unusual bacterially synthesized polyesters. The expanding diversities in structure and the material properties of biopolymers are key for exploring practical applications. The enzyme and metabolic engineering approaches toward this goal are discussed by shedding light on the successful case studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Branding the bio/biomedical engineering degree.

Science.gov (United States)

Voigt, Herbert F

2011-01-01

The future challenges to medical and biological engineering, sometimes referred to as biomedical engineering or simply bioengineering, are many. Some of these are identifiable now and others will emerge from time to time as new technologies are introduced and harnessed. There is a fundamental issue regarding "Branding the bio/biomedical engineering degree" that requires a common understanding of what is meant by a B.S. degree in Biomedical Engineering, Bioengineering, or Biological Engineering. In this paper we address some of the issues involved in branding the Bio/Biomedical Engineering degree, with the aim of clarifying the Bio/Biomedical Engineering brand.

Bioinspiration: applying mechanical design to experimental biology.

Science.gov (United States)

Flammang, Brooke E; Porter, Marianne E

2011-07-01

The production of bioinspired and biomimetic constructs has fostered much collaboration between biologists and engineers, although the extent of biological accuracy employed in the designs produced has not always been a priority. Even the exact definitions of "bioinspired" and "biomimetic" differ among biologists, engineers, and industrial designers, leading to confusion regarding the level of integration and replication of biological principles and physiology. By any name, biologically-inspired mechanical constructs have become an increasingly important research tool in experimental biology, offering the opportunity to focus research by creating model organisms that can be easily manipulated to fill a desired parameter space of structural and functional repertoires. Innovative researchers with both biological and engineering backgrounds have found ways to use bioinspired models to explore the biomechanics of organisms from all kingdoms to answer a variety of different questions. Bringing together these biologists and engineers will hopefully result in an open discourse of techniques and fruitful collaborations for experimental and industrial endeavors.

A new digitized reverse correction method for hypoid gears based on a one-dimensional probe

Science.gov (United States)

Li, Tianxing; Li, Jubo; Deng, Xiaozhong; Yang, Jianjun; Li, Genggeng; Ma, Wensuo

2017-12-01

In order to improve the tooth surface geometric accuracy and transmission quality of hypoid gears, a new digitized reverse correction method is proposed based on the measurement data from a one-dimensional probe. The minimization of tooth surface geometrical deviations is realized from the perspective of mathematical analysis and reverse engineering. Combining the analysis of complex tooth surface generation principles and the measurement mechanism of one-dimensional probes, the mathematical relationship between the theoretical designed tooth surface, the actual machined tooth surface and the deviation tooth surface is established, the mapping relation between machine-tool settings and tooth surface deviations is derived, and the essential connection between the accurate calculation of tooth surface deviations and the reverse correction method of machine-tool settings is revealed. Furthermore, a reverse correction model of machine-tool settings is built, a reverse correction strategy is planned, and the minimization of tooth surface deviations is achieved by means of the method of numerical iterative reverse solution. On this basis, a digitized reverse correction system for hypoid gears is developed by the organic combination of numerical control generation, accurate measurement, computer numerical processing, and digitized correction. Finally, the correctness and practicability of the digitized reverse correction method are proved through a reverse correction experiment. The experimental results show that the tooth surface geometric deviations meet the engineering requirements after two trial cuts and one correction.

Synthetic biology approaches to engineering the nitrogen symbiosis in cereals.

Science.gov (United States)

Rogers, Christian; Oldroyd, Giles E D

2014-05-01

Nitrogen is abundant in the earth's atmosphere but, unlike carbon, cannot be directly assimilated by plants. The limitation this places on plant productivity has been circumvented in contemporary agriculture through the production and application of chemical fertilizers. The chemical reduction of nitrogen for this purpose consumes large amounts of energy and the reactive nitrogen released into the environment as a result of fertilizer application leads to greenhouse gas emissions, as well as widespread eutrophication of aquatic ecosystems. The environmental impacts are intensified by injudicious use of fertilizers in many parts of the world. Simultaneously, limitations in the production and supply of chemical fertilizers in other regions are leading to low agricultural productivity and malnutrition. Nitrogen can be directly fixed from the atmosphere by some bacteria and Archaea, which possess the enzyme nitrogenase. Some plant species, most notably legumes, have evolved close symbiotic associations with nitrogen-fixing bacteria. Engineering cereal crops with the capability to fix their own nitrogen could one day address the problems created by the over- and under-use of nitrogen fertilizers in agriculture. This could be achieved either by expression of a functional nitrogenase enzyme in the cells of the cereal crop or through transferring the capability to form a symbiotic association with nitrogen-fixing bacteria. While potentially transformative, these biotechnological approaches are challenging; however, with recent advances in synthetic biology they are viable long-term goals. This review discusses the possibility of these biotechnological solutions to the nitrogen problem, focusing on engineering the nitrogen symbiosis in cereals.

Cognitive science in the era of artificial intelligence: A roadmap for reverse-engineering the infant language-learner.

Science.gov (United States)

Dupoux, Emmanuel

2018-04-01

Spectacular progress in the information processing sciences (machine learning, wearable sensors) promises to revolutionize the study of cognitive development. Here, we analyse the conditions under which 'reverse engineering' language development, i.e., building an effective system that mimics infant's achievements, can contribute to our scientific understanding of early language development. We argue that, on the computational side, it is important to move from toy problems to the full complexity of the learning situation, and take as input as faithful reconstructions of the sensory signals available to infants as possible. On the data side, accessible but privacy-preserving repositories of home data have to be setup. On the psycholinguistic side, specific tests have to be constructed to benchmark humans and machines at different linguistic levels. We discuss the feasibility of this approach and present an overview of current results. Copyright © 2017 Elsevier B.V. All rights reserved.

Industrial systems biology and its impact on synthetic biology of yeast cell factories.

Science.gov (United States)

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-06-01

Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

QM/MM hybrid calculation of biological macromolecules using a new interface program connecting QM and MM engines

Energy Technology Data Exchange (ETDEWEB)

Hagiwara, Yohsuke; Tateno, Masaru [Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba Science City, Ibaraki 305-8571 (Japan); Ohta, Takehiro [Center for Computational Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba Science City, Ibaraki 305-8577 (Japan)], E-mail: tateno@ccs.tsukuba.ac.jp

2009-02-11

An interface program connecting a quantum mechanics (QM) calculation engine, GAMESS, and a molecular mechanics (MM) calculation engine, AMBER, has been developed for QM/MM hybrid calculations. A protein-DNA complex is used as a test system to investigate the following two types of QM/MM schemes. In a 'subtractive' scheme, electrostatic interactions between QM/MM regions are truncated in QM calculations; in an 'additive' scheme, long-range electrostatic interactions within a cut-off distance from QM regions are introduced into one-electron integration terms of a QM Hamiltonian. In these calculations, 338 atoms are assigned as QM atoms using Hartree-Fock (HF)/density functional theory (DFT) hybrid all-electron calculations. By comparing the results of the additive and subtractive schemes, it is found that electronic structures are perturbed significantly by the introduction of MM partial charges surrounding QM regions, suggesting that biological processes occurring in functional sites are modulated by the surrounding structures. This also indicates that the effects of long-range electrostatic interactions involved in the QM Hamiltonian are crucial for accurate descriptions of electronic structures of biological macromolecules.

Biologically inspired robotic inspectors: the engineering reality and future outlook (Keynote address)

Science.gov (United States)

Bar-Cohen, Yoseph

2005-04-01

Human errors have long been recognized as a major factor in the reliability of nondestructive evaluation results. To minimize such errors, there is an increasing reliance on automatic inspection tools that allow faster and consistent tests. Crawlers and various manipulation devices are commonly used to perform variety of inspection procedures that include C-scan with contour following capability to rapidly inspect complex structures. The emergence of robots has been the result of the need to deal with parts that are too complex to handle by a simple automatic system. Economical factors are continuing to hamper the wide use of robotics for inspection applications however technology advances are increasingly changing this paradigm. Autonomous robots, which may look like human, can potentially address the need to inspect structures with configuration that are not predetermined. The operation of such robots that mimic biology may take place at harsh or hazardous environments that are too dangerous for human presence. Biomimetic technologies such as artificial intelligence, artificial muscles, artificial vision and numerous others are increasingly becoming common engineering tools. Inspired by science fiction, making biomimetic robots is increasingly becoming an engineering reality and in this paper the state-of-the-art will be reviewed and the outlook for the future will be discussed.

Fiscal 1999 achievement report on regional consortium research and development project. Regional consortium activity in its 3rd year (Research and development of reverse engineering system for local craftwork articles); 1999 nendo chiiki kogeihin muke reverse engineering system no kenkyu kaihatsu seika hokokusho. 3

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

The effort concerns Ryukyu craftwork articles. Reverse engineering used to be regarded as a technique of imitation or duplication but today it is drawing attention as a concept of positively utilizing the directionality of information flow in the integrated environment. In the development of a reverse information system, novel designs are created by utilizing a 3-dimensional data base, a high-efficiency fabrication technology for metal patterns for the press-molding of glass is established incorporating some fabrication diagnosing techniques, and a system is constructed under which fabrication accuracy is evaluated and difference data are fed back. In the development of technologies for metal pattern cutting and surface reforming, a metal pattern fabrication technology for molding glass, low in cost and high in performance, is systematized, which enables short delivery. In the diversification of glass products, Ryukyu patterns are collected and Ryukyu glass products are tentatively manufactured by press-molding, and a good result is achieved. In the field of total system technology, basic technologies for an advanced and integrated common production base are established. A virtual reality assisted designing system is developed, under which the designer feels force on the finger tips when preparing a shape for a 3-dimensional structure. (NEDO)

Hybrid chitosan-ß-glycerol phosphate-gelatin nano-/micro fibrous scaffolds with suitable mechanical and biological properties for tissue engineering.

Science.gov (United States)

Lotfi, Marzieh; Bagherzadeh, Roohollah; Naderi-Meshkin, Hojjat; Mahdipour, Elahe; Mafinezhad, Asghar; Sadeghnia, Hamid Reza; Esmaily, Habibollah; Maleki, Masoud; Hasssanzadeh, Halimeh; Ghayaour-Mobarhan, Majid; Bidkhori, Hamid Reza; Bahrami, Ahmad Reza

2016-03-01

Scaffold-based tissue engineering is considered as a promising approach in the regenerative medicine. Graft instability of collagen, by causing poor mechanical properties and rapid degradation, and their hard handling remains major challenges to be addressed. In this research, a composite structured nano-/microfibrous scaffold, made from a mixture of chitosan-ß-glycerol phosphate-gelatin (chitosan-GP-gelatin) using a standard electrospinning set-up was developed. Gelatin-acid acetic and chitosan ß-glycerol phosphate-HCL solutions were prepared at ratios of 30/70, 50/50, 70/30 (w/w) and their mechanical and biological properties were engineered. Furthermore, the pore structure of the fabricated nanofibrous scaffolds was investigated and predicted using a theoretical model. Higher gelatin concentrations in the polymer blend resulted in significant increase in mean pore size and its distribution. Interaction between the scaffold and the contained cells was also monitored and compared in the test and control groups. Scaffolds with higher chitosan concentrations showed higher rate of cell attachment with better proliferation property, compared with gelatin-only scaffolds. The fabricated scaffolds, unlike many other natural polymers, also exhibit non-toxic and biodegradable properties in the grafted tissues. In conclusion, the data clearly showed that the fabricated biomaterial is a biologically compatible scaffold with potential to serve as a proper platform for retaining the cultured cells for further application in cell-based tissue engineering, especially in wound healing practices. These results suggested the potential of using mesoporous composite chitosan-GP-gelatin fibrous scaffolds for engineering three-dimensional tissues with different inherent cell characteristics. © 2015 Wiley Periodicals, Inc.

A Critical Analysis of a Hand Orthosis Reverse Engineering and 3D Printing Process

Directory of Open Access Journals (Sweden)

Gabriele Baronio

2016-01-01

Full Text Available The possibility to realize highly customized orthoses is receiving boost thanks to the widespread diffusion of low-cost 3D printing technologies. However, rapid prototyping (RP with 3D printers is only the final stage of patient personalized orthotics processes. A reverse engineering (RE process is in fact essential before RP, to digitize the 3D anatomy of interest and to process the obtained surface with suitable modeling software, in order to produce the virtual solid model of the orthosis to be printed. In this paper, we focus on the specific and demanding case of the customized production of hand orthosis. We design and test the essential steps of the entire production process with particular emphasis on the accurate acquisition of the forearm geometry and on the subsequent production of a printable model of the orthosis. The choice of the various hardware and software tools (3D scanner, modeling software, and FDM printer is aimed at the mitigation of the design and production costs while guaranteeing suitable levels of data accuracy, process efficiency, and design versatility. Eventually, the proposed method is critically analyzed so that the residual issues and critical aspects are highlighted in order to discuss possible alternative approaches and to derive insightful observations that could guide future research activities.

Design of microreactor by integration of reverse engineering and direct metal laser sintering process

Energy Technology Data Exchange (ETDEWEB)

Bineli, Aulus Roberto Romao; Gimenez Perez, Ana Paula; Bernardes, Luiz Fernando; Munhoz, Andre Luiz Jardini; Maciel Filho, Rubens [Universidade de Campinas (LOPCA/UNICAMP), SP (Brazil). School of Chemical Engineering. Laboratory of Optimization, Design and Advanced Process Control], Email: aulus@feq.unicamp.br

2010-07-01

The propose of this work is to present high precision microfabrication facilities using computer aided technologies as Reverse Engineering (RE) and Rapid Manufacturing (RM) to analyze, design and construct micro reactors to produce high content hydrogen gas. Micro reactors are very compact, have a high surface to volume ratio, exhibit enhanced heat and mass transfer rates, denotes extremely low pressure drop and allow improved thermal integration in the processes involved. The main goals of micro reactors are the optimization of conventional chemical plants and low footprint, opening different ways to research new process technologies and synthesis of new products. In this work, a microchannels plate and housing structure of these plates were fabricated using DMLS method (Direct Metal Laser Sintering). The plates were analyzed to verify the minimum thickness wall that machine can produce, and the housing structure were digitalized, using a 3D scanning, to perform a 3D inspection and to verify the deflection of the constructed part in comparison with original CAD design models. It was observed that DMLS systems are able to produce micro reactors and microchannels plates with high precision at different metallic materials. However, it is important to choose appropriate conditions to avoid residual stresses and consequently warping parts. (author)

Biomolecular engineering for nanobio/bionanotechnology

Science.gov (United States)

Nagamune, Teruyuki

2017-04-01

Biomolecular engineering can be used to purposefully manipulate biomolecules, such as peptides, proteins, nucleic acids and lipids, within the framework of the relations among their structures, functions and properties, as well as their applicability to such areas as developing novel biomaterials, biosensing, bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be used to design and tune the sizes, shapes, properties and functionality of nanomaterials. As such, there are considerable overlaps between nanotechnology and biomolecular engineering, in that both are concerned with the structure and behavior of materials on the nanometer scale or smaller. Therefore, in combination with nanotechnology, biomolecular engineering is expected to open up new fields of nanobio/bionanotechnology and to contribute to the development of novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights recent studies using engineered biological molecules (e.g., oligonucleotides, peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and ligands) combined with functional nanomaterials in nanobio/bionanotechnology applications, including therapeutics, diagnostics, biosensing, bioanalysis and biocatalysts. Furthermore, this review focuses on five areas of recent advances in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering, (c) protein engineering, (d) chemical and enzymatic conjugation technologies, and (e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and nanobiosystems are anticipated to emerge as next-generation platforms for bioelectronics, biosensors, biocatalysts, molecular imaging modalities, biological actuators, and biomedical applications.

Microscale technologies for cell engineering

CERN Document Server

Gaharwar, Akhilesh

2016-01-01

This book offers readers cutting-edge research at the interface of polymer science and engineering, biomedical engineering, materials science, and biology. State-of-the-art developments in microscale technologies for cell engineering applications are covered, including technologies relevant to both pluripotent and adult stem cells, the immune system, and somatic cells of the animal and human origin. This book bridges the gap in the understanding of engineering biology at multiple length scale, including microenvironmental control, bioprocessing, and tissue engineering in the areas of cardiac, cartilage, skeletal, and vascular tissues, among others. This book also discusses unique, emerging areas of micropatterning and three-dimensional printing models of cellular engineering, and contributes to the better understanding of the role of biophysical factors in determining the cell fate. Microscale Technologies for Cell Engineering is valuable for bioengineers, biomaterial scientists, tissue engineers, clinicians,...

Advances in biomedical engineering

CERN Document Server

Brown, J H U

1976-01-01

Advances in Biomedical Engineering, Volume 6, is a collection of papers that discusses the role of integrated electronics in medical systems and the usage of biological mathematical models in biological systems. Other papers deal with the health care systems, the problems and methods of approach toward rehabilitation, as well as the future of biomedical engineering. One paper discusses the use of system identification as it applies to biological systems to estimate the values of a number of parameters (for example, resistance, diffusion coefficients) by indirect means. More particularly, the i

Social smile reproducibility using 3-D stereophotogrammetry and reverse engineering technology.

Science.gov (United States)

Dindaroğlu, Furkan; Duran, Gökhan Serhat; Görgülü, Serkan; Yetkiner, Enver

2016-05-01

To assess the range of social smile reproducibility using 3-D stereophotogrammetry and reverse engineering technology. Social smile images of white adolescents (N  =  15, mean age  =  15.4 ±1.5 years; range  =  14-17 years) were obtained using 3dMDFlex (3dMD, Atlanta, Ga). Each participant was asked to produce 16 social smiles at 3-minute intervals. All images were obtained in natural head position. Alignment of images, segmentation of smile area, and 3-D deviation analysis were carried out using Geomagic Control software (3D Systems Inc, Cary, NC). A single image was taken as a reference, and the remaining 15 images were compared with the reference image to evaluate positive and negative deviations. The differences between the mean deviation limits of participants with the highest and the lowest deviations and the total mean deviations were evaluated using Bland-Altman Plots. Minimum and maximum deviations of a single image from the reference image were 0.34 and 2.69 mm, respectively. Lowest deviation between two images was within 0.5 mm and 1.54 mm among all participants (mean, 0.96 ± 0.21 mm), and the highest deviation was between 0.41 mm and 2.69 mm (mean, 1.53 ± 0.46 mm). For a single patient, when all alignments were considered together, the mean deviation was between 0.32 ± 0.10 mm and 0.59 ± 0.24 mm. Mean deviation for one image was between 0.14 and 1.21 mm. The range of reproducibility of the social smile presented individual variability, but this variation was not clinically significant or detectable under routine clinical observation.

NDE in biomedical engineering

International Nuclear Information System (INIS)

Bhagwat, Aditya; Kumar, Pradeep

2015-01-01

Biomedical Engineering (BME) is an interdisciplinary field, marking the conjunction of Medical and Engineering disciplines. It combines the design and problem solving skills of engineering with medical and biological sciences to advance health care treatment, including diagnosis, monitoring, and therapy

Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

Science.gov (United States)

Kunkle, Brian W.; Yoo, Changwon; Roy, Deodutta

2013-01-01

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors. PMID:23737970

Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

Directory of Open Access Journals (Sweden)

Brian W Kunkle

Full Text Available In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV, and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated. These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

VI Latin American Congress on Biomedical Engineering

CERN Document Server

Hadad, Alejandro

2015-01-01

This volume presents the proceedings of the CLAIB 2014, held in Paraná, Entre Ríos, Argentina 29, 30 & 31 October 2014. The proceedings, presented by the Regional Council of Biomedical Engineering for Latin America (CORAL) offer research findings, experiences and activities between institutions and universities to develop Bioengineering, Biomedical Engineering and related sciences. The conferences of the American Congress of Biomedical Engineering are sponsored by the International Federation for Medical and Biological Engineering (IFMBE), Society for Engineering in Biology and Medicine (EMBS) and the Pan American Health Organization (PAHO), among other organizations and international agencies and bringing together scientists, academics and biomedical engineers in Latin America and other continents in an environment conducive to exchange and professional growth. The Topics include: - Bioinformatics and Computational Biology - Bioinstrumentation; Sensors, Micro and Nano Technologies - Biomaterials, Tissu...

Redox-induced reversible luminescence switching of cerium-doped upconversion nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Huang, Yanan [College of Sciences, Shanghai University, Shanghai 200444 (China); International Laboratory for Adaptive Bio-nanotechnology, Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Science, Suzhou 215123 (China); Xiao, Qingbo, E-mail: qbxiao2011@sinano.ac.cn [International Laboratory for Adaptive Bio-nanotechnology, Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Science, Suzhou 215123 (China); Wang, Jian [College of Sciences, Shanghai University, Shanghai 200444 (China); International Laboratory for Adaptive Bio-nanotechnology, Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Science, Suzhou 215123 (China); Xi, Yonglan [Laboratory for Agricultural Wastes Treatment and Recycling Institute of Agricultural Resources and Environment, Jiangsu Academy of Agricultural Science, Nanjing 210014 (China); Li, Fujin [International Laboratory for Adaptive Bio-nanotechnology, Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Science, Suzhou 215123 (China); Feng, Yamin [College of Sciences, Shanghai University, Shanghai 200444 (China); International Laboratory for Adaptive Bio-nanotechnology, Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Science, Suzhou 215123 (China); Shi, Liyi [College of Sciences, Shanghai University, Shanghai 200444 (China); Lin, Hongzhen, E-mail: hzlin2010@sinano.ac.cn [International Laboratory for Adaptive Bio-nanotechnology, Suzhou Institute of Nano-tech and Nano-bionics (SINANO), Chinese Academy of Science, Suzhou 215123 (China)

2016-05-15

Smart upconversion nanophosphors (UCNPs) that can be reversibly switched between two or more luminescent states by certain external stimuli have attracted considerable attention due to their great potential in biological applications. Here we report for the first time a type of redox-switchable UCNPs by codoping NaGdF{sub 4}:Yb/Er nanorods with the redox-active Ce{sup 3+}/Ce{sup 4+} ion pairs. A reversible switching of their UC luminescence intensity was observed upon the variation of the surrounding redox environments. We show solid proof that the luminescence switching is caused by the tailoring of the NaGdF{sub 4} host crystal structure in response to changing redox state of the codoped cerium ions. A proof-of-concept example is further demonstrated by using these UCNPs for probing the dynamical variation of redox environments in biological tissues. - Highlights: • Synthesis of upconversion nanoparticles doped with Ce{sup 3+}/Ce{sup 4+} ions. • The precise and reversible modification of crystal structure by redox reactions. • Tuning the upconversion luminescence by tailoring the crystal structure.

Effective multiple oral administration of reverse genetics engineered infectious bursal disease virus in mice in the presence of neutralizing antibodies.

Science.gov (United States)

Hornyák, Ákos; Lipinski, Kai S; Bakonyi, Tamás; Forgách, Petra; Horváth, Ernő; Farsang, Attila; Hedley, Susan J; Palya, Vilmos; Bakács, Tibor; Kovesdi, Imre

2015-01-01

Despite spectacular successes in hepatitis B and C therapies, severe hepatic impairment is still a major treatment problem. The clinically tested infectious bursal disease virus (IBDV) superinfection therapy promises an innovative, interferon-free solution to this great unmet need, provided that a consistent manufacturing process preventing mutations or reversions to virulent strains is obtained. To address safety concerns, a tissue culture adapted IBDV vaccine strain V903/78 was cloned into cDNA plasmids ensuring reproducible production of a reverse engineered virus R903/78. The therapeutic drug candidate was characterized by immunocytochemistry assay, virus particle determination and immunoblot analysis. The biodistribution and potential immunogenicity of the IBDV agent was determined in mice, which is not a natural host of this virus, by quantitative detection of IBDV RNA by a quantitative reverse transcriptase-polymerase chain reaction and virus neutralization test, respectively. Several human cell lines supported IBDV propagation in the absence of visible cytopathic effect. The virus was stable from pH 8 to pH 6 and demonstrated significant resistance to low pH and also proved to be highly resistant to high temperatures. No pathological effects were observed in mice. Single and multiple oral administration of IBDV elicited antibodies with neutralizing activities in vitro. Repeat oral administration of R903/78 was successful despite the presence of neutralizing antibodies. Single oral and intravenous administration indicated that IBDV does not replicate in mammalian liver alleviating some safety related concerns. These data supports the development of an orally delivered anti-hepatitis B virus/ anti-hepatitis C virus viral agent for human use. Copyright © 2015 John Wiley & Sons, Ltd.

Two-photon fluorescent polysiloxane-based films with thermally responsive self switching properties achieved by a unique reversible spirocyclization mechanism.

Science.gov (United States)

Zuo, Yujing; Yang, Tingxin; Zhang, Yu; Gou, Zhiming; Tian, Minggang; Kong, Xiuqi; Lin, Weiying

2018-03-14

Responsiveness and reversibility are present in nature, and are ubiquitous in biological systems. The realization of reversibility and responsiveness is of great importance in the development of properties and the design of new materials. However, two-photon fluorescent thermal-responsive materials have not been reported to date. Herein, we engineered thermally responsive polysiloxane materials ( Dns-non ) that exhibited unique two-photon luminescence, and this is the first report about thermally responsive luminescent materials with two-photon fluorescence. The fluorescence of Dns-non could switch from the "on" to "off" state through a facile heating and cooling process, which could be observed by the naked eye. Monitoring the temperature of the CPU in situ was achieved by easily coating D1-non onto the CPU surface, which verified the potential application in devices of Dns-non . A unique alkaline tuned reversible transition mechanism of rhodamine-B from its spirocyclic to its ring-open state was proposed. Furthermore, Dns-non appeared to be a useful cell adhesive for the culture of cells on the surface. We believe that the constructed thermally responsive silicon films which have promising utilization as a new type of functional fluorescent material, may show broad applications in materials chemistry or bioscience.

Genome scale engineering techniques for metabolic engineering.

Science.gov (United States)

Liu, Rongming; Bassalo, Marcelo C; Zeitoun, Ramsey I; Gill, Ryan T

2015-11-01

Metabolic engineering has expanded from a focus on designs requiring a small number of genetic modifications to increasingly complex designs driven by advances in genome-scale engineering technologies. Metabolic engineering has been generally defined by the use of iterative cycles of rational genome modifications, strain analysis and characterization, and a synthesis step that fuels additional hypothesis generation. This cycle mirrors the Design-Build-Test-Learn cycle followed throughout various engineering fields that has recently become a defining aspect of synthetic biology. This review will attempt to summarize recent genome-scale design, build, test, and learn technologies and relate their use to a range of metabolic engineering applications. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Metabolic Engineering X Conference

Energy Technology Data Exchange (ETDEWEB)

Flach, Evan [American Institute of Chemical Engineers

2015-05-07

The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

Chemical Engineering in the "BIO" world

DEFF Research Database (Denmark)

Chiarappa, Gianluca; Grassi, Mario; Abrami, Michela

2017-01-01

Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical...... engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering...... baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy...

Engineering Parameters in Bioreactor's Design: A Critical Aspect in Tissue Engineering

Science.gov (United States)

Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

2013-01-01

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors. PMID:24000327

Engineering parameters in bioreactor's design: a critical aspect in tissue engineering.

Science.gov (United States)

Salehi-Nik, Nasim; Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Anisi, Fatemeh; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

2013-01-01

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

Performance of tubular reverse osmosis for the desalination ...

African Journals Online (AJOL)

Municipal solid waste leachate (MSWL) has the potential to pollute the water environment and to affect biological treatment processes adversely if not properly handled. Reverse osmosis (RO) has the ability to remove both organics and inorganics effectively from effluents. Therefore, RO was evaluated for the treatment of ...

Systems Biology of Industrial Microorganisms

Science.gov (United States)

Papini, Marta; Salazar, Margarita; Nielsen, Jens

The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

Synthetic biological networks

International Nuclear Information System (INIS)

Archer, Eric; Süel, Gürol M

2013-01-01

Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

Impact of environmental inputs on reverse-engineering approach to network structures.

Science.gov (United States)

Wu, Jianhua; Sinfield, James L; Buchanan-Wollaston, Vicky; Feng, Jianfeng

2009-12-04

Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs. With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. We first represent the environmental inputs by a harmonic oscillator and combine them with Granger causality to identify environmental inputs and then uncover the causal network structures. We also generalize it to multiple harmonic oscillators to represent various exogenous influences. This system approach is extensively tested with toy models and successfully applied to a real biological network of microarray data of the flowering genes of the model plant Arabidopsis Thaliana. The aim is to identify those genes that are directly affected by the presence of the sunlight and uncover the interactive network structures associating with flowering metabolism. We demonstrate that environmental inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations.

A comparison of ROChem reverse osmosis and spiral wound reverse osmosis membrane modules

International Nuclear Information System (INIS)

Siler, J.L.

1992-01-01

Testing of the ROChem Disc Tube reg-sign reverse osmosis (RO) module's performance on biologically active feed waters has been completed. Both the ROChem module (using Filmtec standard-rejection seawater membranes) and the Filmtec spiral-wound membrane module (using Filmtec high-rejection seawater membranes) were tested with stimulant solutions containing typical bacteria and metal hydroxide levels found in the F/H Effluent Treatment Facility (ETF) influent. Results indicate that the ROChem module gave superior performance over the spiral-wound module. Water flux losses were reduced by over 30% for water recoveries above 40%

Identification of cysteine proteases and screening of cysteine protease inhibitors in biological samples by a two-dimensional gel system of zymography and reverse zymography.

Science.gov (United States)

Saitoh, Eiichi; Yamamoto, Shinya; Okamoto, Eishiro; Hayakawa, Yoshimi; Hoshino, Takashi; Sato, Ritsuko; Isemura, Satoko; Ohtsubo, Sadami; Taniguchi, Masayuki

2007-11-18

We have developed a two-dimensional (2D-) gel system of zymography and reverse zymography for the detection and characterization of proteases and protease inhibitors. Isoelectric focusing (IEF) agarose gels with pH gradients were employed for separation in the first-dimension and sodium dodecyl sulfate (SDS)-polyacrylamide gel copolymerized with gelatin used for the second dimension. Proteases and protease inhibitors separated by IEF gel were applied on the second gel without trichloroacetic acid (TCA) fixation. Protease activity in the 2D-gel was visualized as transparent spots where gelatin substrate was digested after commassie brilliant blue (CBB) staining. Some of the transparent spots from the skin mucus extract of rainbow trout were determined to be a cysteine protease through use of E-64 or CA-074. In the reverse zymography technique, the gel was incubated with papain solution at 37 degrees C for 18 h. Cysteine protease inhibitors from broad bean seeds were detected as clear blue spots after CBB staining. The amino (N-) terminal sequences of four papain inhibitor spots thus detected were demonstrated to be identical to that of favin beta chain, a broad bean lectin. Taken together, our system can be considered to be an efficient technique for discovering and characterizing new proteases and protease inhibitors in biological samples. This is the first report describing a 2D-gel system of zymography and reverse zymography.

Computing the Reverse Eccentric Connectivity Index for Certain Family of Nanocone and Fullerene Structures

Directory of Open Access Journals (Sweden)

Wei Gao

2016-01-01

Full Text Available A large number of previous works reveal that there exist strong connections between the chemical characteristics of chemical compounds and drugs (e.g., melting point and boiling point and their topological structures. Chemical indices introduced on these molecular topological structures can help chemists and material and medical scientists to grasp its chemical reactivity, biological activity, and physical features better. Hence, the study of the topological indices on the material structure can make up the defect of experiments and provide the theoretical evidence in material engineering. In this paper, we determine the reverse eccentric connectivity index of one family of pentagonal carbon nanocones PCN5[n] and three infinite families of fullerenes C12n+2,  C12n+4, and C18n+10 based on graph analysis and computation derivation, and these results can offer the theoretical basis for material properties.

Developments in the Tools and Methodologies of Synthetic Biology

Science.gov (United States)

Kelwick, Richard; MacDonald, James T.; Webb, Alexander J.; Freemont, Paul

2014-01-01

Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a “body of knowledge” from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community. PMID:25505788

Developments in the tools and methodologies of synthetic biology

Directory of Open Access Journals (Sweden)

Richard eKelwick

2014-11-01

Full Text Available Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices or systems. However, biological systems are generally complex and unpredictable and are therefore intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a ‘body of knowledge’ from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled and its functionality tested. At each stage of the design cycle an expanding repertoire of tools is being developed. In this review we highlight several of these tools in terms of their applications and benefits to the synthetic biology community.

Engineering Parameters in Bioreactor’s Design: A Critical Aspect in Tissue Engineering

Directory of Open Access Journals (Sweden)

Nasim Salehi-Nik

2013-01-01

Full Text Available Bioreactors are important inevitable part of any tissue engineering (TE strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

Biotin Switch Assays for Quantitation of Reversible Cysteine Oxidation.

Science.gov (United States)

Li, R; Kast, J

2017-01-01

Thiol groups in protein cysteine residues can be subjected to different oxidative modifications by reactive oxygen/nitrogen species. Reversible cysteine oxidation, including S-nitrosylation, S-sulfenylation, S-glutathionylation, and disulfide formation, modulate multiple biological functions, such as enzyme catalysis, antioxidant, and other signaling pathways. However, the biological relevance of reversible cysteine oxidation is typically underestimated, in part due to the low abundance and high reactivity of some of these modifications, and the lack of methods to enrich and quantify them. To facilitate future research efforts, this chapter describes detailed procedures to target the different modifications using mass spectrometry-based biotin switch assays. By switching the modification of interest to a biotin moiety, these assays leverage the high affinity between biotin and avidin to enrich the modification. The use of stable isotope labeling and a range of selective reducing agents facilitate the quantitation of individual as well as total reversible cysteine oxidation. The biotin switch assay has been widely applied to the quantitative analysis of S-nitrosylation in different disease models and is now also emerging as a valuable research tool for other oxidative cysteine modifications, highlighting its relevance as a versatile, robust strategy for carrying out in-depth studies in redox proteomics. © 2017 Elsevier Inc. All rights reserved.

Opportunities for Merging Chemical and Biological Synthesis

Science.gov (United States)

Wallace, Stephen; Balskus, Emily P.

2014-01-01

Organic chemists and metabolic engineers use largely orthogonal technologies to access small molecules like pharmaceuticals and commodity chemicals. As the use of biological catalysts and engineered organisms for chemical production grows, it is becoming increasingly evident that future efforts for chemical manufacture will benefit from the integration and unified expansion of these two fields. This review will discuss approaches that combine chemical and biological synthesis for small molecule production. We highlight recent advances in combining enzymatic and non-enzymatic catalysis in vitro, discuss the application of design principles from organic chemistry for engineering non-biological reactivity into enzymes, and describe the development of biocompatible chemistry that can be interfaced with microbial metabolism. PMID:24747284

Synthetic Biology for Specialty Chemicals.

Science.gov (United States)

Markham, Kelly A; Alper, Hal S

2015-01-01

In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications

International Nuclear Information System (INIS)

Xu Tao; Binder, Kyle W; Albanna, Mohammad Z; Dice, Dennis; Zhao Weixin; Yoo, James J; Atala, Anthony

2013-01-01

Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin–collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation

KAUST Repository

Deng, Yue

2017-08-05

Motivation: The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. Results: We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes.

Reversed-field multiple mirror concept

International Nuclear Information System (INIS)

Steinhauer, L.C.; Grossmann, W.; Seyler, C.E.

1978-01-01

The reversed-field multiple mirror (RFMM), is a promising technique for end-stoppering linear magnetic fusion plasmas. By this means the physics and engineering advantages of a linear plasma are gained while circumventing the endloss problem, allowing the projection of very short (less than or equal to 100 m) conceptual reactors. RFMM end-stoppering is accomplished by a string of closed field-line cells on the plasma column axis; these cells strongly retard the axial flow of particles and energy. We describe the reactor implications of the RFMM

Glycosylation Engineering

DEFF Research Database (Denmark)

Clausen, Henrik; Wandall, Hans H.; Steentoft, Catharina

2017-01-01

Knowledge of the cellular pathways of glycosylation across phylogeny provides opportunities for designing glycans via genetic engineering in a wide variety of cell types including bacteria, fungi, plant cells, and mammalian cells. The commercial demand for glycosylation engineering is broad......, including production of biological therapeutics with defined glycosylation (Chapter 57). This chapter describes how knowledge of glycan structures and their metabolism (Parts I–III of this book) has led to the current state of glycosylation engineering in different cell types. Perspectives for rapid...

Monoamines stimulate sex reversal in the saddleback wrasse.

Science.gov (United States)

Larson, Earl T; Norris, David O; Gordon Grau, E; Summers, Cliff H

2003-02-15

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a

Computational Modeling in Tissue Engineering

CERN Document Server

2013-01-01

One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

GRASP/Ada: Graphical Representations of Algorithms, Structures, and Processes for Ada. The development of a program analysis environment for Ada: Reverse engineering tools for Ada, task 2, phase 3

Science.gov (United States)

Cross, James H., II

1991-01-01

The main objective is the investigation, formulation, and generation of graphical representations of algorithms, structures, and processes for Ada (GRASP/Ada). The presented task, in which various graphical representations that can be extracted or generated from source code are described and categorized, is focused on reverse engineering. The following subject areas are covered: the system model; control structure diagram generator; object oriented design diagram generator; user interface; and the GRASP library.

Cell and Tissue Engineering

CERN Document Server

2012-01-01

“Cell and Tissue Engineering” introduces the principles and new approaches in cell and tissue engineering. It includes both the fundamentals and the current trends in cell and tissue engineering, in a way useful both to a novice and an expert in the field. The book is composed of 13 chapters all of which are written by the leading experts. It is organized to gradually assemble an insight in cell and tissue function starting form a molecular nano-level, extending to a cellular micro-level and finishing at the tissue macro-level. In specific, biological, physiological, biophysical, biochemical, medical, and engineering aspects are covered from the standpoint of the development of functional substitutes of biological tissues for potential clinical use. Topics in the area of cell engineering include cell membrane biophysics, structure and function of the cytoskeleton, cell-extracellular matrix interactions, and mechanotransduction. In the area of tissue engineering the focus is on the in vitro cultivation of ...

Where Are All the Women Engineers? An Insider's View of Socialization and Power in Engineering Education

Science.gov (United States)

Christman, Jeanne

2017-01-01

Despite more than thirty years of the underrepresentation of women in engineering being a persistent concern, research on the cause of the problem has not been successful in reversing the trend. A plethora of theories as to why females are not entering engineering exist, yet they only address issues on the surface and do not attend to a…

Preparing Synthetic Biology for the World

Directory of Open Access Journals (Sweden)

Gerd H.G. Moe-Behrens

2013-01-01

Full Text Available Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or living devices. As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space? In this review, we explain how studies of genetically modified organisms lay groundwork for the future landscape of biosafety. Early in the design process, biological engineers are anticipating potential hazards and developing innovative tools to mitigate risk. Here, we survey lessons learned, ongoing efforts to engineer intrinsic biocontainment, and how different stakeholders in synthetic biology can act to accomplish best practices for biosafety.

Translational systems biology: introduction of an engineering approach to the pathophysiology of the burn patient.

Science.gov (United States)

An, Gary; Faeder, James; Vodovotz, Yoram

2008-01-01

The pathophysiology of the burn patient manifests the full spectrum of the complexity of the inflammatory response. In the acute phase, inflammation may have negative effects via capillary leak, the propagation of inhalation injury, and development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care research. Conversely, inflammation is a necessary prologue and component in the later stage processes of wound healing. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens. Translational systems biology (TSB) is the application of dynamic mathematical modeling and certain engineering principles to biological systems to integrate mechanism with phenomenon and, importantly, to revise clinical practice. This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research.

VII Latin American Congress on Biomedical Engineering

CERN Document Server

Bustamante, John; Sierra, Daniel

2017-01-01

This volume presents the proceedings of the CLAIB 2016, held in Bucaramanga, Santander, Colombia, 26, 27 & 28 October 2016. The proceedings, presented by the Regional Council of Biomedical Engineering for Latin America (CORAL), offer research findings, experiences and activities between institutions and universities to develop Bioengineering, Biomedical Engineering and related sciences. The conferences of the American Congress of Biomedical Engineering are sponsored by the International Federation for Medical and Biological Engineering (IFMBE), Society for Engineering in Biology and Medicine (EMBS) and the Pan American Health Organization (PAHO), among other organizations and international agencies to bring together scientists, academics and biomedical engineers in Latin America and other continents in an environment conducive to exchange and professional growth.

Systems biology solutions for biochemical production challenges

DEFF Research Database (Denmark)

Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus

2017-01-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics...... characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity...... compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains...

Engineering synergy in biotechnology

DEFF Research Database (Denmark)

Nielsen, Jens; Fussenegger, Martin; Keasling, Jay

2014-01-01

In this article, the author focuses on approaches in metabolic engineering and synthetic biology for the creation of efficient cell factories, which can be bused to convert biomass and other feedstocks for the generation of chemicals. Topics discussed include development of restriction enzymes......, engineering plasmids and recyclable markers, production of 1,3-propanediol using a metabolically engineered Escherichia coli and production of isobutanol by using metabolically engineered yeast....

Energy Efficient Engine program advanced turbofan nacelle definition study

Science.gov (United States)

Howe, David C.; Wynosky, T. A.

1985-01-01

Advanced, low drag, nacelle configurations were defined for some of the more promising propulsion systems identified in the earlier Benefit/Cost Study, to assess the benefits associated with these advanced technology nacelles and formulate programs for developing these nacelles and low volume thrust reversers/spoilers to a state of technology readiness in the early 1990's. The study results established the design feasibility of advanced technology, slim line nacelles applicable to advanced technology, high bypass ratio turbofan engines. Design feasibility was also established for two low volume thrust reverse/spoiler concepts that meet or exceed the required effectiveness for these engines. These nacelle and thrust reverse/spoiler designs were shown to be applicable in engines with takeoff thrust sizes ranging from 24,000 to 60,000 pounds. The reduced weight, drag, and cost of the advanced technology nacelle installations relative to current technology nacelles offer a mission fuel burn savings ranging from 3.0 to 4.5 percent and direct operating cost plus interest improvements from 1.6 to 2.2 percent.

Three-dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation

OpenAIRE

Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna; Iliuk, Anton; Tao, W. Andy

2016-01-01

Glycoproteins have vast structural diversity which plays an important role in many biological processes and have great potential as disease biomarkers. Here we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase GlycoProtein Array (polyGPA), to specifically capture and profile glycoproteomes, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture pre-oxidized glycan...

Reversible flowchart languages and the structured reversible program theorem

DEFF Research Database (Denmark)

Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

2008-01-01

Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow...... operators. Reversible flowcharts are r- Turing-complete, meaning that they can simuluate reversible Turing machines without garbage data. We also demonstrate the injectivization of classical flowcharts into reversible flowcharts. The reversible flowchart computation model provides a theoretical...

EDWARDS' REFERENCE CYCLE FOR INTERNAL AND EXTERNAL COMBUSTION ENGINES

OpenAIRE

A. E. Piir

2014-01-01

Useful physical regularities of a reversible thermodynamic cycle for heat engines have been established in the paper. The engines are using fuel combustion products as a heat source, and the environment - as a heat sink that surpasses Carnot cycle according to efficiency factor.

Biosynthesis of therapeutic natural products using synthetic biology.

Science.gov (United States)

Awan, Ali R; Shaw, William M; Ellis, Tom

2016-10-01

Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthetic biology between technoscience and thing knowledge.

Science.gov (United States)

Gelfert, Axel

2013-06-01

Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called 'thing knowledge'. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world-knowledge that, in turn, can be accessed via continuous experimental interrogation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Toward scalable parts families for predictable design of biological circuits.

Science.gov (United States)

Lucks, Julius B; Qi, Lei; Whitaker, Weston R; Arkin, Adam P

2008-12-01

Our current ability to engineer biological circuits is hindered by design cycles that are costly in terms of time and money, with constructs failing to operate as desired, or evolving away from the desired function once deployed. Synthetic biologists seek to understand biological design principles and use them to create technologies that increase the efficiency of the genetic engineering design cycle. Central to the approach is the creation of biological parts--encapsulated functions that can be composited together to create new pathways with predictable behaviors. We define five desirable characteristics of biological parts--independence, reliability, tunability, orthogonality and composability, and review studies of small natural and synthetic biological circuits that provide insights into each of these characteristics. We propose that the creation of appropriate sets of families of parts with these properties is a prerequisite for efficient, predictable engineering of new function in cells and will enable a large increase in the sophistication of genetic engineering applications.

Synthetic Biology: Putting Synthesis into Biology

Science.gov (United States)

Liang, Jing; Luo, Yunzi; Zhao, Huimin

2010-01-01

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

Cigarette company trade secrets are not secret: an analysis of reverse engineering reports in internal tobacco industry documents released as a result of litigation.

Science.gov (United States)

Velicer, Clayton; Lempert, Lauren K; Glantz, Stanton

2015-09-01

Use previously secret tobacco industry documents to assess tobacco companies' routine claims of trade secret protection for information on cigarette ingredients, additives and construction made to regulatory agencies, as well as the companies' refusal to publicly disclose this information. We analysed previously secret tobacco industry documents available at (http://legacy.library.ucsf.edu) to identify 100 examples of seven major tobacco companies' reverse engineering of their competitors' brands between 1937 and 2001. These reverse engineering reports contain detailed data for 142 different measurements for at least two companies, including physical parameters of the cigarettes, tobacco types, humectants, additives, flavourings, and smoke constituents of competitors' cigarettes. These 100 documents were distributed to 564 employees, including top managers in domestic and foreign offices across multiple departments, including executive leadership, research and design, product development, marketing and legal. These documents reported new competitors' products, measured ingredient changes over time, and informed companies' decisions regarding ingredients in their own products. Because cigarette companies routinely analyse their competitors' cigarettes in great detail, this information is neither secret nor commercially valuable and, thus, does not meet the legal definition of a 'trade secret.' This information is only being kept 'secret' from the people consuming cigarettes and the scientific community. Public agencies should release this detailed information because it would provide valuable information about how ingredients affect addictiveness and toxicity, and would help the public health community and consumers better understand the impact of cigarette design on human health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Synthetic Biology: Knowledge Accessed by Everyone (Open Sources)

Science.gov (United States)

Sánchez Reyes, Patricia Margarita

2016-01-01

Using the principles of biology, along with engineering and with the help of computer, scientists manage to copy. DNA sequences from nature and use them to create new organisms. DNA is created through engineering and computer science managing to create life inside a laboratory. We cannot dismiss the role that synthetic biology could lead in…

Solid-phase synthesis of protein-polymers on reversible immobilization supports.

Science.gov (United States)

Murata, Hironobu; Carmali, Sheiliza; Baker, Stefanie L; Matyjaszewski, Krzysztof; Russell, Alan J

2018-02-27

Facile automated biomacromolecule synthesis is at the heart of blending synthetic and biologic worlds. Full access to abiotic/biotic synthetic diversity first occurred when chemistry was developed to grow nucleic acids and peptides from reversibly immobilized precursors. Protein-polymer conjugates, however, have always been synthesized in solution in multi-step, multi-day processes that couple innovative chemistry with challenging purification. Here we report the generation of protein-polymer hybrids synthesized by protein-ATRP on reversible immobilization supports (PARIS). We utilized modified agarose beads to covalently and reversibly couple to proteins in amino-specific reactions. We then modified reversibly immobilized proteins with protein-reactive ATRP initiators and, after ATRP, we released and analyzed the protein polymers. The activity and stability of PARIS-synthesized and solution-synthesized conjugates demonstrated that PARIS was an effective, rapid, and simple method to generate protein-polymer conjugates. Automation of PARIS significantly reduced synthesis/purification timelines, thereby opening a path to changing how to generate protein-polymer conjugates.

Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

Science.gov (United States)

Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

2013-04-01

The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetic dissection of behavioral flexibility: reversal learning in mice.

Science.gov (United States)

Laughlin, Rick E; Grant, Tara L; Williams, Robert W; Jentsch, J David

2011-06-01

Behavioral inflexibility is a feature of schizophrenia, attention-deficit/hyperactivity disorder, and behavior addictions that likely results from heritable deficits in the inhibitory control over behavior. Here, we investigate the genetic basis of individual differences in flexibility, measured using an operant reversal learning task. We quantified discrimination acquisition and subsequent reversal learning in a cohort of 51 BXD strains of mice (2-5 mice/strain, n = 176) for which we have matched data on sequence, gene expression in key central nervous system regions, and neuroreceptor levels. Strain variation in trials to criterion on acquisition and reversal was high, with moderate heritability (∼.3). Acquisition and reversal learning phenotypes did not covary at the strain level, suggesting that these traits are effectively under independent genetic control. Reversal performance did covary with dopamine D2 receptor levels in the ventral midbrain, consistent with a similar observed relationship between impulsivity and D2 receptors in humans. Reversal, but not acquisition, is linked to a locus on mouse chromosome 10 with a peak likelihood ratio statistic at 86.2 megabase (p work demonstrates the clear trait independence between, and genetic control of, discrimination acquisition and reversal and illustrates how globally coherent data sets for a single panel of highly related strains can be interrogated and integrated to uncover genetic sources and molecular and neuropharmacological candidates of complex behavioral traits relevant to human psychopathology. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Reverse Algols

Science.gov (United States)

Leung, K. C.

1989-01-01

Reverse Algols, binary systems with a semidetached configuration in which the more massive component is in contact with the critical equipotential surface, are examined. Observational evidence for reverse Algols is presented and the parameters of seven reverse Algols are listed. The evolution of Algols and reverse Algols is discussed. It is suggested that, because reverse Algols represent the premass-reversal semidetached phase of close binary evolution, the evolutionary time scale between regular and reverse Algols is the ratio of the number of confirmed systems of these two Algol types.

Biological responses to acidification reversal in Cumbrian streamwaters - stream water chemistry

Energy Technology Data Exchange (ETDEWEB)

Tipping, E.; Hardie, D.J.; Lawlor, A.J.; Lofts, S.; Simon, B.M.; Vincent, C.D. [Institute of Freshwater Ecology, Ambleside (United Kingdom)

1999-07-01

This reports summarises the findings of a study sampling the streams for invertebrates and comparing the results with those made in the 1960s and 1970s, The distribution of the bacterium Cytophaga was examined, and the results of the chemical analysis of the stream waters were compared with the results from previous years. The background to the study is traced, and details of the sampling and chemical analysis are given. Evidence of the reversal of acidification in the streams is considered.

Bioinspired Hydrogels to Engineer Cancer Microenvironments.

Science.gov (United States)

Park, Kyung Min; Lewis, Daniel; Gerecht, Sharon

2017-06-21

Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes. In this review, we discuss the development and use of polymeric hydrogel materials to engineer native tumor ECMs for cancer research, focusing on emerging technologies in cancer engineering that aim to accelerate clinical outcomes.

Opportunities in Biological Sciences; [VGM Career Horizons Series].

Science.gov (United States)

Winter, Charles A.

This book provides job descriptions and discusses career opportunities in various fields of the biological sciences. These fields include: (1) biotechnology, genetics, biomedical engineering, microbiology, mycology, systematic biology, marine and aquatic biology, botany, plant physiology, plant pathology, ecology, and wildlife biology; (2) the…

Molecular Cloning Designer Simulator (MCDS): All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects.

Science.gov (United States)

Shi, Zhenyu; Vickers, Claudia E

2016-12-01

Molecular Cloning Designer Simulator (MCDS) is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1) it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2) it can perform a user-defined workflow of cloning steps in a single execution of the software; (3) it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4) it includes experimental information to conveniently guide wet lab work; and (5) it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com.

Quantum Stirling heat engine and refrigerator with single and coupled spin systems

Science.gov (United States)

Huang, Xiao-Li; Niu, Xin-Ya; Xiu, Xiao-Ming; Yi, Xue-Xi

2014-02-01

We study the reversible quantum Stirling cycle with a single spin or two coupled spins as the working substance. With the single spin as the working substance, we find that under certain conditions the reversed cycle of a heat engine is NOT a refrigerator, this feature holds true for a Stirling heat engine with an ion trapped in a shallow potential as its working substance. The efficiency of quantum Stirling heat engine can be higher than the efficiency of the Carnot engine, but the performance coefficient of the quantum Stirling refrigerator is always lower than its classical counterpart. With two coupled spins as the working substance, we find that a heat engine can turn to a refrigerator due to the increasing of the coupling constant, this can be explained by the properties of the isothermal line in the magnetic field-entropy plane.

Fractionation of chromium(III) compounds in biological matrices

Energy Technology Data Exchange (ETDEWEB)

Knoechel, A.; Weseloh, G. [Institute of Inorganic and Applied Chemistry, University of Hamburg (Germany)

1999-03-01

Many details of the metabolism and biological significance of trivalent inorganic cations have remained obscure up to now, not least because of the lack of appropriate tools for species analysis of these cations in biological matrices. In order to demonstrate the capabilities of reversed-phase ion-pair chromatography, the distribution of chromium species in brewer`s yeast, previously incubated with radiolabelled {sup 51}Cr chloride was investigated. Contradictory to the findings of most other researchers in this area, two low-molecular weight, anionic chromium species were detected in cytosolic yeast extracts. In conclusion, reversed-phase ion-pair chromatography may reveal new details of intracellular metabolism of chromium(III) and, possibly, other trivalent cations. (orig.) With 1 fig., 16 refs.

Concise Review: Organ Engineering: Design, Technology, and Integration.

Science.gov (United States)

Kaushik, Gaurav; Leijten, Jeroen; Khademhosseini, Ali

2017-01-01

Engineering complex tissues and whole organs has the potential to dramatically impact translational medicine in several avenues. Organ engineering is a discipline that integrates biological knowledge of embryological development, anatomy, physiology, and cellular interactions with enabling technologies including biocompatible biomaterials and biofabrication platforms such as three-dimensional bioprinting. When engineering complex tissues and organs, core design principles must be taken into account, such as the structure-function relationship, biochemical signaling, mechanics, gradients, and spatial constraints. Technological advances in biomaterials, biofabrication, and biomedical imaging allow for in vitro control of these factors to recreate in vivo phenomena. Finally, organ engineering emerges as an integration of biological design and technical rigor. An overall workflow for organ engineering and guiding technology to advance biology as well as a perspective on necessary future iterations in the field is discussed. Stem Cells 2017;35:51-60. © 2016 AlphaMed Press.

Structural Interfaces and Attachments in Biology

CERN Document Server

Birman, Victor; Genin, Guy

2013-01-01

Attachment of dissimilar materials in engineering and surgical practice is a perennial challenge. Bimaterial attachment sites are common locations for injury, repeated injury, and mechanical failure. Nature presents several highly effective solutions to the challenge of bimaterial attachment that differ from those found in engineering practice. Structural Interfaces and Attachments in Biology describes the attachment of dissimilar materials from multiple perspectives. The text will simultaneously elucidate natural bimaterial attachments and outline engineering principles underlying successful attachments to the communities of tissue engineers and surgeons. Included an in-depth analysis of the biology of attachments in the body and mechanisms by which robust attachments are formed, a review of current concepts of attaching dissimilar materials in surgical practice and a discussion of bioengineering approaches that are currently being developed. This book also: Provides the first comprehensive treatment of phys...

Managing Reverse Logistics or Reversing Logistics Management?

OpenAIRE

Brito, Marisa

2004-01-01

textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

Systems biology solutions for biochemical production challenges.

Science.gov (United States)

Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

2017-06-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fast switching of bistable magnetic nanowires through collective spin reversal

Science.gov (United States)

Vindigni, Alessandro; Rettori, Angelo; Bogani, Lapo; Caneschi, Andrea; Gatteschi, Dante; Sessoli, Roberta; Novak, Miguel A.

2005-08-01

The use of magnetic nanowires as memory units is made possible by the exponential divergence of the characteristic time for magnetization reversal at low temperature, but the slow relaxation makes the manipulation of the frozen magnetic states difficult. We suggest that finite-size segments can show a fast switching if collective reversal of the spins is taken into account. This mechanism gives rise at low temperatures to a scaling law for the dynamic susceptibility that has been experimentally observed for the dilute molecular chain Co(hfac)2NitPhOMe. These results suggest a possible way of engineering nanowires for fast switching of the magnetization.

Agent-based modelling in synthetic biology.

Science.gov (United States)

Gorochowski, Thomas E

2016-11-30

Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

Opportunities in plant synthetic biology.

Science.gov (United States)

Cook, Charis; Martin, Lisa; Bastow, Ruth

2014-05-01

Synthetic biology is an emerging field uniting scientists from all disciplines with the aim of designing or re-designing biological processes. Initially, synthetic biology breakthroughs came from microbiology, chemistry, physics, computer science, materials science, mathematics, and engineering disciplines. A transition to multicellular systems is the next logical step for synthetic biologists and plants will provide an ideal platform for this new phase of research. This meeting report highlights some of the exciting plant synthetic biology projects, and tools and resources, presented and discussed at the 2013 GARNet workshop on plant synthetic biology.

Toroidal fusion reactor design based on the reversed-field pinch

International Nuclear Information System (INIS)

Hagenson, R.L.

1978-07-01

The toroidal reversed-field pinch (RFP) achieves gross equilibrium and stability with a combination of high shear and wall stabilization, rather than the imposition of tokamak-like q-constraints. Consequently, confinement is provided primarily by poloidal magnetic fields, poloidal betas as large as approximately 0.58 are obtainable, the high ohmic-heating (toroidal) current densities promise a sole means of heating a D-T plasma to ignition, and the plasma aspect ratio is not limited by stability/equilibrium constraints. A reactor-like plasma model has been developed in order to quantify and to assess the general features of a power system based upon RFP confinement. An ''operating point'' has been generated on the basis of this plasma model and a relatively detailed engineering energy balance. These results are used to generate a conceptual engineering model of the reversed-field pinch reactor (RFPR) which includes a general description of a 750 MWe power plant and the preliminary consideration of vacuum/fueling, first wall, blanket, magnet coils, iron core, and the energy storage/transfer system

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

Science.gov (United States)

Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

2015-07-06

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

Science.gov (United States)

Dyment, Nathaniel A.; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Butler, David L.

2015-01-01

The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair. PMID:25266738

Systems Biology-an interdisciplinary approach.

Science.gov (United States)

Friboulet, Alain; Thomas, Daniel

2005-06-15

System-level approaches in biology are not new but foundations of "Systems Biology" are achieved only now at the beginning of the 21st century [Kitano, H., 2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed interest for a system-level approach is linked to the progress in collecting experimental data and to the limits of the "reductionist" approach. System-level understanding of native biological and pathological systems is needed to provide potential therapeutic targets. Examples of interdisciplinary approach in Systems Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic engineering and idiotypic networks are discussed in the framework of Systems Biology.

Bio Engineering Laboratory

Data.gov (United States)

Federal Laboratory Consortium — Description/History: Chemistry and biology laboratoriesThe Bio Engineering Laboratory (BeL) is theonly full spectrum biotechnology capability within the Department...

Transmission mode acoustic time-reversal imaging for nondestructive evaluation

Science.gov (United States)

Lehman, Sean K.; Devaney, Anthony J.

2002-11-01

In previous ASA meetings and JASA papers, the extended and formalized theory of transmission mode time reversal in which the transceivers are noncoincident was presented. When combined with the subspace concepts of a generalized MUltiple SIgnal Classification (MUSIC) algorithm, this theory is used to form super-resolution images of scatterers buried in a medium. These techniques are now applied to ultrasonic nondestructive evaluation (NDE) of parts, and shallow subsurface seismic imaging. Results are presented of NDE experiments on metal and epoxy blocks using data collected from an adaptive ultrasonic array, that is, a ''time-reversal machine,'' at Lawrence Livermore National Laboratory. Also presented are the results of seismo-acoustic subsurface probing of buried hazardous waste pits at the Idaho National Engineering and Environmental Laboratory. [Work performed under the auspices of the U.S. Department of Energy by University of California Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48.] [Work supported in part by CenSSIS, the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the NSF (award number EEC-9986821) as well as from Air Force Contracts No. F41624-99-D6002 and No. F49620-99-C0013.

Biological science in conservation

Science.gov (United States)

David M. Johns

2000-01-01

Large-scale wildlands reserve systems offer one of the best hopes for slowing, if not reversing, the loss of biodiversity and wilderness. Establishing such reserves requires both sound biology and effective advocacy. Attempts by The Wildlands Project and its cooperators to meld science and advocacy in the service of conservation is working, but is not without some...

Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

Directory of Open Access Journals (Sweden)

Ching CTS

2012-02-01

Full Text Available Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA, and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc, five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group, 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second

Probenazole treatment inhibits anthocyanins biosynthesis via ...

African Journals Online (AJOL)

ELO

2012-01-05

Jan 5, 2012 ... State Key Laboratory of Genetic Engineering and Institute of Plant Biology, School of Life .... was reverse-transcribed with SuperScript reverse transcriptase ..... treated plant have more drought and salt stress tolerance.

Thermostability of biological systems: fundamentals, challenges, and quantification.

Science.gov (United States)

He, Xiaoming

2011-01-01

This review examines the fundamentals and challenges in engineering/understanding the thermostability of biological systems over a wide temperature range (from the cryogenic to hyperthermic regimen). Applications of the bio-thermostability engineering to either destroy unwanted or stabilize useful biologicals for the treatment of diseases in modern medicine are first introduced. Studies on the biological responses to cryogenic and hyperthermic temperatures for the various applications are reviewed to understand the mechanism of thermal (both cryo and hyperthermic) injury and its quantification at the molecular, cellular and tissue/organ levels. Methods for quantifying the thermophysical processes of the various applications are then summarized accounting for the effect of blood perfusion, metabolism, water transport across cell plasma membrane, and phase transition (both equilibrium and non-equilibrium such as ice formation and glass transition) of water. The review concludes with a summary of the status quo and future perspectives in engineering the thermostability of biological systems.

Opposition-Based Memetic Algorithm and Hybrid Approach for Sorting Permutations by Reversals.

Science.gov (United States)

Soncco-Álvarez, José Luis; Muñoz, Daniel M; Ayala-Rincón, Mauricio

2018-02-21

Sorting unsigned permutations by reversals is a difficult problem; indeed, it was proved to be NP-hard by Caprara (1997). Because of its high complexity, many approximation algorithms to compute the minimal reversal distance were proposed until reaching the nowadays best-known theoretical ratio of 1.375. In this article, two memetic algorithms to compute the reversal distance are proposed. The first one uses the technique of opposition-based learning leading to an opposition-based memetic algorithm; the second one improves the previous algorithm by applying the heuristic of two breakpoint elimination leading to a hybrid approach. Several experiments were performed with one-hundred randomly generated permutations, single benchmark permutations, and biological permutations. Results of the experiments showed that the proposed OBMA and Hybrid-OBMA algorithms achieve the best results for practical cases, that is, for permutations of length up to 120. Also, Hybrid-OBMA showed to improve the results of OBMA for permutations greater than or equal to 60. The applicability of our proposed algorithms was checked processing permutations based on biological data, in which case OBMA gave the best average results for all instances.

Aspergilli: Systems biology and industrial applications

DEFF Research Database (Denmark)

Knuf, Christoph; Nielsen, Jens

2012-01-01

possible to implement systems biology tools to advance metabolic engineering. These tools include genome-wide transcription analysis and genome-scale metabolic models. Herein, we review achievements in the field and highlight the impact of Aspergillus systems biology on industrial biotechnology....

Space Synthetic Biology (SSB)

Data.gov (United States)

National Aeronautics and Space Administration — This project focused on employing advanced biological engineering and bioelectrochemical reactor systems to increase life support loop closure and in situ resource...

Ethics of Reproductive Engineering

Science.gov (United States)

Buuck, R. John

1977-01-01

Artificial insemination, in vitro fertilization, artificial placentas, and cloning are examined from a ethical viewpoint. The moral, social, and legal implications of reproductive engineering are considered important to biology as well as medicine. The author suggests that these ethical issues should be included in the biology curriculum and lists…

Experimental studies of field-reversed configuration translation

Energy Technology Data Exchange (ETDEWEB)

Rej, D.J.; Armstrong, W.T.; Chrien, R.E.; Klingner, P.L.; Linford, R.K.; McKenna, K.F.; Sherwood, E.G.; Siemon, R.E.; Tuszewski, M.; Milroy, R.D.

1986-03-01

In the FRX-C/T experiment (Proceedings of the 9th Symposium for Engineering Problems of Fusion Research (IEEE, New York, 1981), p. 1751), field-reversed configuration (FRC) plasmas have been formed in, and launched from, a field-reversed theta-pinch source and subsequently trapped in an adjacent confinement region. No destructive instabilities or enhanced losses of poloidal flux, particles, or thermal energy are observed for FRC total trajectories of up to 16 m. The observed translation dynamics agree with two-dimensional magnetohydrodynamic (MHD) simulations. When translated into reduced external magnetic fields, FRC's are observed to accelerate, expand, and cool in partial agreement with adiabatic theory. The plasmas reflect from an external mirror and after each reflection, the axial kinetic energy is reduced by approximately 50%. Because of this reduction, FRC's are readily trapped without the need of pulsed gate magnet coils.

Engineering a lunar photolithoautotroph to thrive on the moon - life or simulacrum?

Science.gov (United States)

Ellery, A. A.

2018-07-01

Recent work in developing self-replicating machines has approached the problem as an engineering problem, using engineering materials and methods to implement an engineering analogue of a hitherto uniquely biological function. The question is - can anything be learned that might be relevant to an astrobiological context in which the problem is to determine the general form of biology independent of the Earth. Compared with other non-terrestrial biology disciplines, engineered life is more demanding. Engineering a self-replicating machine tackles real environments unlike artificial life which avoids the problem of physical instantiation altogether by examining software models. Engineering a self-replicating machine is also more demanding than synthetic biology as no library of functional components exists. Everything must be constructed de novo. Biological systems already have the capacity to self-replicate but no engineered machine has yet been constructed with the same ability - this is our primary goal. On the basis of the von Neumann analysis of self-replication, self-replication is a by-product of universal construction capability - a universal constructor is a machine that can construct anything (in a functional sense) given the appropriate instructions (DNA/RNA), energy (ATP) and materials (food). In the biological cell, the universal construction mechanism is the ribosome. The ribosome is a biological assembly line for constructing proteins while DNA constitutes a design specification. For a photoautotroph, the energy source is ambient and the food is inorganic. We submit that engineering a self-replicating machine opens up new areas of astrobiology to be explored in the limits of life.

Synthetic biology, inspired by synthetic chemistry.

Science.gov (United States)

Malinova, V; Nallani, M; Meier, W P; Sinner, E K

2012-07-16

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Engineering properties of the crude oil–contaminated soils of Niger ...

African Journals Online (AJOL)

There was a reverse trend when soil samples with appreciable percentages of sand and crude oil of low THC were used. The knowledge of these will aid geotechnical engineers on their designs and remediation techniques. Keywords: Engineering properties, soils, crude oil, hydrocarbon, Niger Delta, Nigeria ...

Gas engine driven reversible heat pumps: Innovative design. Realizzazione di una pompa di calore reversibile azionata da motore a gas

Energy Technology Data Exchange (ETDEWEB)

Canci, F.; Zecchin, M.

1992-01-01

This paper describes the development of a series of gas engine driven air-water compression heat pumps designed for reversible summer-winter operation. The development work was carried out within the framework of a joint venture combing the efforts of the Italian Gas Society, Natural Gas of Barcellona and Climaveneta of Vicenza (Italy), who acted as the heat pump constructor. The main objective of this venture was to develop a series of machines that would be suitable for the contemporaneous summer air conditioning and winter space heating of medium-sized buildings. The designs were optimized to allow cost and energy savings with respect to conventional equipment. The useful cooling power range of the innovative heat pump systems goes from 100 to 250 kW thus giving them the flexibility not yet afforded by conventional equipment currently sold on international markets. In addition to pointing out the new heat pumps' main design and performance features, this paper suggests some feasible applications.

Reverse Logistics

OpenAIRE

Kulikova, Olga

2016-01-01

This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

Inferring Broad Regulatory Biology from Time Course Data: Have We Reached an Upper Bound under Constraints Typical of In Vivo Studies?

Directory of Open Access Journals (Sweden)

Saurabh Vashishtha

Full Text Available There is a growing appreciation for the network biology that regulates the coordinated expression of molecular and cellular markers however questions persist regarding the identifiability of these networks. Here we explore some of the issues relevant to recovering directed regulatory networks from time course data collected under experimental constraints typical of in vivo studies. NetSim simulations of sparsely connected biological networks were used to evaluate two simple feature selection techniques used in the construction of linear Ordinary Differential Equation (ODE models, namely truncation of terms versus latent vector projection. Performance was compared with ODE-based Time Series Network Identification (TSNI integral, and the information-theoretic Time-Delay ARACNE (TD-ARACNE. Projection-based techniques and TSNI integral outperformed truncation-based selection and TD-ARACNE on aggregate networks with edge densities of 10-30%, i.e. transcription factor, protein-protein cliques and immune signaling networks. All were more robust to noise than truncation-based feature selection. Performance was comparable on the in silico 10-node DREAM 3 network, a 5-node Yeast synthetic network designed for In vivo Reverse-engineering and Modeling Assessment (IRMA and a 9-node human HeLa cell cycle network of similar size and edge density. Performance was more sensitive to the number of time courses than to sample frequency and extrapolated better to larger networks by grouping experiments. In all cases performance declined rapidly in larger networks with lower edge density. Limited recovery and high false positive rates obtained overall bring into question our ability to generate informative time course data rather than the design of any particular reverse engineering algorithm.

Harmonic uniflow engine

Science.gov (United States)

Bennett, Charles L.

2016-03-22

A reciprocating-piston uniflow engine includes a harmonic oscillator inlet valve capable of oscillating at a resonant frequency for controlling the flow of working fluid into the engine. In particular, the inlet valve includes an inlet valve head and a spring arranged together as a harmonic oscillator so that the inlet valve head is moveable from an unbiased equilibrium position to a biased closed position occluding an inlet. When released, the inlet valve head undergoes a single oscillation past the equilibrium position to a maximum open position and returns to a biased return position close to the closed position to choke the flow and produce a pressure drop across the inlet valve causing the inlet valve to close. In other embodiments, the harmonic oscillator arrangement of the inlet valve enables the uniflow engine to be reversibly operated as a uniflow compressor.

Distinct difference in relative biological effectiveness of 252Cf neutrons for the induction of mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila melanogaster

International Nuclear Information System (INIS)

Yoshikawa, Isao; Hoshi, Masaharu; Ikenaga, Mituo

1996-01-01

The relative biological effectiveness (RBE) of 252 Cf neutrons was determined for two different types of somatic mutations, i.e., loss of heterozygosity for wing-hair mutations and reversion of the mutant white-ivory eye-color, in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change in the white locus on the X-chromosome. For a quantitative comparison of RBE values for these events, we have constructed a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clones can be detected simultaneously in the same individuals. Larvae were irradiated at the age of 80±4 h post-oviposition with 252 Cf neutrons or 137 Cs γ-rays, and male adult flies were examined under the microscope for the presence of the two types of clonal mosaic spots appearing. The induction of wing-hair spots per dose unit was much greater for 252 Cf neutrons than for 137 Cs γ -rays, whereas the frequencies of eye-color reversion were similar for neutrons and γ-rays. The estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant wing-hair spots and revertant eye-color spots, respectively. These results indicate that the RBE of neutrons is much greater for mitotic crossing over in comparison to the intragenic white-ivory reversion events. Possible causes for the difference in RBE are discussed

Nanodimensional and Nanocrystalline Apatites and Other Calcium Orthophosphates in Biomedical Engineering, Biology and Medicine

Directory of Open Access Journals (Sweden)

Sergey V. Dorozhkin

2009-11-01

Full Text Available Recent developments in biomineralization have already demonstrated that nanosized particles play an important role in the formation of hard tissues of animals. Namely, the basic inorganic building blocks of bones and teeth of mammals are nanodimensional and nanocrystalline calcium orthophosphates (in the form of apatites of a biological origin. In mammals, tens to hundreds nanocrystals of a biological apatite were found to be combined into self-assembled structures under the control of various bioorganic matrixes. In addition, the structures of both dental enamel and bones could be mimicked by an oriented aggregation of nanosized calcium orthophosphates, determined by the biomolecules. The application and prospective use of nanodimensional and nanocrystalline calcium orthophosphates for a clinical repair of damaged bones and teeth are also known. For example, a greater viability and a better proliferation of various types of cells were detected on smaller crystals of calcium orthophosphates. Thus, the nanodimensional and nanocrystalline forms of calcium orthophosphates have a great potential to revolutionize the field of hard tissue engineering starting from bone repair and augmentation to the controlled drug delivery devices. This paper reviews current state of knowledge and recent developments of this subject starting from the synthesis and characterization to biomedical and clinical applications. More to the point, this review provides possible directions of future research and development.

Nature-inspired computation in engineering

CERN Document Server

2016-01-01

This timely review book summarizes the state-of-the-art developments in nature-inspired optimization algorithms and their applications in engineering. Algorithms and topics include the overview and history of nature-inspired algorithms, discrete firefly algorithm, discrete cuckoo search, plant propagation algorithm, parameter-free bat algorithm, gravitational search, biogeography-based algorithm, differential evolution, particle swarm optimization and others. Applications include vehicle routing, swarming robots, discrete and combinatorial optimization, clustering of wireless sensor networks, cell formation, economic load dispatch, metamodeling, surrogated-assisted cooperative co-evolution, data fitting and reverse engineering as well as other case studies in engineering. This book will be an ideal reference for researchers, lecturers, graduates and engineers who are interested in nature-inspired computation, artificial intelligence and computational intelligence. It can also serve as a reference for relevant...

The Science of Solubility: Using Reverse Engineering to Brew a Perfect Cup of Coffee

Science.gov (United States)

West, Andrew B.; Sickel, Aaron J.; Cribbs, Jennifer D.

2015-01-01

The Next Generation Science Standards call for the integration of science and engineering. Often, the introduction of engineering activities occurs after instruction in the science content. That is, engineering is used as a way for students to elaborate on science ideas that have already been explored. However, using only this sequence of…

Varieties of noise: analogical reasoning in synthetic biology.

Science.gov (United States)

Knuuttila, Tarja; Loettgers, Andrea

2014-12-01

The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice.

Evaluation of Biological Toxicity of CdTe Quantum Dots with Different Coating Reagents according to Protein Expression of Engineering Escherichia coli

Directory of Open Access Journals (Sweden)

Wei Xu

2015-01-01

Full Text Available The results obtained from toxicity assessment of quantum dots (QDs can be used to establish guidelines for the application of QDs in bioimaging. This paper focused on the design of a novel method to evaluate the toxicity of CdTe QDs using engineering Escherichia coli as a model. The toxicity of mercaptoacetic acid (MPA, glutathione (GSH, and L-cysteine (Cys capped CdTe QDs was analyzed according to the heterologous protein expression in BL21/DE3, engineering Escherichia coli extensively used for protein expression. The results showed that the MPA-CdTe QDs had more serious toxicity than the other two kinds of CdTe QDs. The microscopic images and SEM micrographs further proved that both the proliferation and the protein expression of engineering Escherichia coli were inhibited after treatment with MPA-CdTe QDs. The proposed method is important to evaluate biological toxicity of both QDs and other nanoparticles.

Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.